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Drug-eluting 27-29 cheap 100mg caverta visa erectile dysfunction shots,31 buy 50 mg caverta visa impotence diagnosis code,47 balloons offer lower restenosis rates than balloon angioplasty and may provide a durable result with or without atherectomy in regions where stents should be avoided discount caverta 50 mg overnight delivery doctor for erectile dysfunction in dubai, such as over joints. Interventionalists need to establish systems to monitor patients for recurrent or new disease and treat atherosclerosis risk factors intensively. Collaboration with surgical colleagues and vascular medicine specialists should improve outcomes. Tibial Disease The popliteal artery divides into three tibial arteries: the anterior tibial, which becomes the dorsalis pedis in the foot; the posterior tibial, which forms the pedal arcade with the anterior tibial artery; and the peroneal artery, which usually ends just above the ankle but can be an important collateral to the foot. In general, claudication is rare with loss of even two of the three tibial arteries. Catheter-based interventions have high rates of restenosis, in part because of the small diameter and long lesion length, and are rarely justified in patients with claudication. Frequently, correction of obstructive proximal disease will resolve the claudication even with extensive residual tibial disease. Vascular access is more limited for distal tibial 10 disease, because a contralateral femoral approach or a brachial approach (see Fig. A pedal access site may become a nonhealing ulcer if the intervention is 10 unsuccessful, so this approach is often used as a last resort. A, Proximal occlusion of the anterior tibial artery (arrow) with no flow into the foot. C, Balloon angioplasty of the whole anterior tibial artery (the image shows a balloon at the proximal anterior tibial artery). Angiosome-directed revascularization refers to revascularization of a tibial artery that supplies the 10 area of a nonhealing ulcer or gangrene (Fig. The value of angiosome-directed revascularization versus restoring any straight flow to the foot is debated. In observational studies, wound healing was better and amputation lower with angiosome-directed rather than indirect (nonangiosome) tibial 48 revascularization. These observations may be confounded, however, because indirect revascularization 10 may be a marker for more complex tibial disease and poorer limb outcomes. In one study, changes in foot microcirculation assessed by skin perfusion pressures improved to a similar degree in angiosome 49 and nonangiosome tibial revascularization. Although balloon-expandable coronary stents are used, they are prone to external compression. Most of these studies do not show an effect on major amputation or survival, but they may be underpowered for these endpoints. As mentioned, newer drug-coated balloons are under development and testing for tibial interventions. Multiple catheter-based interventions over several months may be required to heal an ulcer because restenosis slows healing. Once healed, however, restenosis may be less of an issue, given the use of adequate foot care and protection to prevent skin breakdown. Gangrenous toes can be left dry until they mummify and autoamputate or can be surgically amputated once viable and devitalized tissue are clearly demarcated. These complexities mandate a team approach to care that includes wound specialists, podiatrists, surgeons, and prosthesis specialists for optimum management. Cervical Artery Disease Extracranial Carotid Disease Extracranial disease of the internal and common carotid artery is a potential source of artery-to-artery embolism, one of the causes of ischemic stroke (see Chapter 65). Over the last two decades, improvements in catheter-based techniques have enabled patients at increased risk for stroke from this 11 cause to be treated with outcomes similar to those of traditional carotid endarterectomy. Symptoms are the most important factor related to the risk for disabling stroke and the indication for revascularization. In the carotid circulation, symptoms are typically dysphasia, contralateral hemiparesis or hemiparesthesia, or 54 ipsilateral transient monocular blindness (amaurosis fugax). Minor strokes are classified as “mild clinical 54 deficits” or “no clinical residual deficits” with evidence of infarction on imaging. The second factor related to stroke risk is the severity of stenosis of the extracranial internal carotid artery. For patients with recent symptoms and stenosis greater than 70%, the risk for stroke over the 5,11,54 subsequent 5 years is up to 30%, with a risk of approximately 10% within the first 3 months. After 3 months, however, the risk for stroke declines and approaches the risk in asymptomatic patients with a 55 similar degree of stenosis (2% to 3% per year). Carotid endarterectomy and stenting both entail a small procedural/operative risk for stroke, and this limits their benefit to patients at low risk for perioperative events but at higher risk for stroke in the long term without revascularization (Tables 66. Based on trials of surgery versus medical therapy from 20 years ago, carotid endarterectomy is recommended for symptomatic patients with greater than 50% to 99% stenosis by invasive angiography or greater than 70% stenosis by noninvasive imaging and 5,11,54 with a periprocedural risk for stroke and death of less than 6%. For asymptomatic patients, indications include 80% to 99% stenosis in those with a periprocedural risk for stroke or death of less 5,11 than 3%. Long-term follow-up of randomized trials show no difference in outcomes over 5 to 10 years between surgical endarterectomy and carotid stenting 56,57 for symptomatic and asymptomatic patients with carotid disease. Acceptably low periprocedural risk 5,55,60 depends on adequate training of operators and selection of patients at low risk for complications. Potential indications for carotid stenting are the same as those listed earlier for endarterectomy. As with endarterectomy, several factors determine the success of carotid stenting. Patient selection is very important in asymptomatic patients or those several months after symptoms, who have a lower absolute 5,11 benefit from surgical endarterectomy or stenting than those with recent symptoms. In asymptomatic patients, the reduction in risk with revascularization accrues slowly over the long term and needs to offset the small but important periprocedural/operative risk. This benefit usually takes several years to accrue, and asymptomatic patients need to have reasonable 5-year survival for a realistic chance of achieving a net benefit from revascularization. For carotid stenting, this 55 includes patients without severe vessel tortuosity, heavy calcification, or significant cognitive deficits. Patients older than 80 years have a higher risk for perioperative adverse events with stenting or surgery. Carotid stenting starts with access to the common carotid artery with a diagnostic catheter and then a delivery sheath. Embolic protection consists of distal protection using filters or obstructive balloons deployed distal to the carotid stenosis or proximal occlusion devices deployed proximal to the stenosis. Filters allow blood flow to the brain to continue and theoretically lead to less brain ischemia if the circle of Willis is incomplete. There is crossover filling through the anterior communicating artery into the left anterior cerebral artery because of poor left-sided perfusion from the left cervical internal carotid stenosis. Vertebral and Subclavian Disease The left and right vertebral arteries usually arise from the left and right subclavian arteries, course through the upper vertebrae into the posterior of the skull, and join together as the basilar artery.
The dorsal approach is well suited for this operation and begins with an incision extending from the 12th rib to the iliac crest along the lateral edge of the sacrospinalis muscle and quadratus lumborum muscle purchase caverta 50mg without a prescription erectile dysfunction pump.com. The dorsolumbar fascia is opened order cheapest caverta and caverta erectile dysfunction needle injection, exposing Gerota’s fascia and the perinephric fat (Fig generic caverta 100 mg amex impotence guilt. The kidney is delivered out of the incision, which is then closed by approximating the dorsolumbar fascia and the fascia of the sacrospinalis muscle. It is performed for small renal cell carcinomas and benign tumors of the kidney, such as angiomyolipomas, and for duplicated collecting systems with a diseased moiety. If the partial nephrectomy is being done for renal cell carcinoma, it may be accompanied with a regional lymphadenectomy. Control of the renal vessels and local hypothermia with ice slush is advised for control of bleeding, if excessive. Incision in the renal parenchyma is made by sharp and blunt dissection, suture-ligating all bleeders. After complete hemostasis, Gelfoam, thrombin, Floseal,or perinephric fat is used to cover the raw surface of the kidney. Radical nephrectomy is the surgical excision of the kidney with its surrounding perinephric fat and Gerota’s fascia and the proximal 2/3 of the ureter, accompanied by paracaval or para-aortic lymphadenectomy. Early control of renal vessels is advised before excessive manipulation of the tumor to minimize blood loss and hematogenous spread. Surgery in patients with renal vein or inferior vena cava involvement is more complex and prone to more intraoperative complications, including blood loss. When the tumor thrombus involves a large segment of the vena cava or is in the right atrium, a team approach with cardiac surgeons is used. Typically, the patient is placed in a flank position as in an open radical nephrectomy. This procedure can be either transperitoneal or retroperitoneal, depending on the surgeon’s preference or experience. The transperitoneal approach may be modified by using a hand-assistance device through one of the ports (hand-assisted laparoscopic nephrectomy). Nephroureterectomy is a radical nephrectomy with ureter resection, including the ureteral orifice and a cuff of bladder wall around it. It is accompanied by a regional lymphadenectomy because it is performed for a cancerous condition. The approach is either transabdominal or extraperitoneal through an extended flank incision, starting at the tip of the 11th rib and curving caudally along the lateral edge of the rectus abdominis muscle down to the pubic bone (Fig. Some surgeons prefer two separate incisions: a flank incision for the radical nephrectomy part and a lower abdominal incision for the ureterectomy. This procedure can be done by laparoscopy with a lower midline incision made to remove the specimen. The kidney is removed laparoscopically while the distal ureter is excised by open surgery. This technique involves positioning, prepping, and draping the patient twice during the case. Specific procedures include the following: Pyeloplasty is the surgical correction of congenital ureteropelvic junction stenosis to relieve obstruction. The most commonly used is the dismembered pyeloplasty, or Anderson-Heinz pyeloplasty, wherein the diseased ureteropelvic junction is excised, the redundant renal pelvis is reduced, and an anastomosis is established between the renal pelvis and ureter (Fig. Usual preop diagnosis: Ureteropelvic junction obstruction Pyelolithotomy and ureterolithotomy are used to remove calculi from the renal pelvis or ureter. The upper ureter and renal pelvis are exposed, usually through a flank approach, the calculus is palpated, and an incision is made in the ureter or renal pelvis over the calculus, which is then delivered. Usual preop diagnosis: Renal pelvic or ureteral stone Transureteroureterostomy is the transposition of one ureter across the midline and anastomosing it to the other ureter (Fig. This operation is performed whenever the distal ureter is traumatized or diseased, and the proximal ureter is not long enough to reimplant into the bladder. Preop evaluation should be directed toward the detection and treatment of these conditions prior to anesthesia. Regional techniques (spinal or epidural) may be alternatives for some open procedures but are less than optimal because of awkward positioning that may → patient discomfort and pain resulting from diaphragmatic stimulation. Simple cystectomy is performed for benign conditions of the bladder, such as severe hemorrhagic cystitis, radiation cystitis, and contracted bladder. The peritoneal reflections are incised down to the pouch of Douglas; the vasa deferentia and superior vesical arteries are identified, cross- clamped, transected, and tied. The ureters are identified, separated from the surrounding tissues, cross-clamped near the bladder, transected, and tied. The bladder is bluntly separated from the anterior rectal wall all the way to the apex of the prostate. The endopelvic fascia is incised, separating the prostate from the lateral pelvic wall. The puboprostatic ligaments are transected, and the dorsal vein of the penis is suture-ligated. The tied dorsal vein and urethra are incised just distal to the apex of the prostate. The specimen is delivered out of the incision and hemostasis secured with electrocautery. Partial cystectomy is the excision of only the part of the bladder containing the pathology. This is not a commonly performed operation and is reserved for tumors located in the dome of the bladder of older patients who are poor surgical risks for major operations, such as radical cystectomy. Beginning with a lower abdominal incision, the dome and lateral walls of the bladder are separated from the surrounding tissues, which are covered by wet packs to minimize contamination. An incision is made in the dome of the bladder at least 2 cm away from the pathology. The incision in the bladder is continued around, and at least 2 cm away from, the pathology, until the latter is completely excised. The bladder wall is then closed in two layers—a through-and- through layer and an inverting layer—using absorbable material. Wet packs are removed, a drain is left in the region, and the abdominal incision is closed. Radical cystectomy (or radical cystoprostatectomy) is performed for treatment of invasive bladder cancer. Itencompasses the removal of the bladder and the lower ureters, the prostate gland, and seminal vesicles in men (Fig. Accompanied by a pelvic lymphadenectomy, it is performed in the supine position, except when a concomitant urethrectomy is required, wherein a lithotomy position is used. Anatomy of the pelvis with tissue to be excised outlined by dashed line: A: male; B: female. Following cystectomy, whether radical or simple, some form of urinary diversion is required.
Local anesthet- low lipid solubility that blocks nerve ﬁbers involved in pain ics block the generation and the conduction of nerve im- transmission (Aδ and C ﬁbers) to a greater degree than pulses by increasing the threshold for electrical excitation those controlling motor function (Aβ ﬁbers) discount caverta 50mg free shipping erectile dysfunction treatment with exercise. The drug in the nerve cheap 100 mg caverta overnight delivery erectile dysfunction joke, by slowing propagation of the nerve impulse purchase caverta in india erectile dysfunction from steroids, was less cardiotoxic than equal concentrations of racemic and by reducing the rate of rise of the action potential. Clinically, the order of loss of nerve function (mean maximum tolerated unbound arterial plasma con- is as follows: (1) pain, (2) temperature, (3) touch, (4) pro- centrations were 0. The drug had an efﬁcacy generally similar to that of the Plasma-protein binding of levobupivacaine evaluated same dose of bupivacaine with regard to pain relief but in vitro was found to be greater than 97% at concentrations caused less motor blockade at low concentrations. The association of levobupiva- caine with human blood cells was very low (0–2%) over the Levobupivacaine concentration range 0. The volume of distribution of levobupivacaine Levobupivacaine injection contains a single enantiomer of after intravenous administration was 67 liters. In and it is related chemically and pharmacologically to the 14 vitro studies using [ C]levobupivacaine showed that amino amide class of local anesthetics (Figure 2-8). Met- The solubility of levobupivacaine hydrochloride in abolic inversion of levobupivacaine to R( )-bupivacaine water is about 100 mg/ml at 20°C, and the partition coef- was not evident both in vitro and in vivo. Of this 95%, about 71% was in Levobupivacaine is a sterile, nonpyrogenic, colorless urine, whereas 24% was in feces. Levobupivacaine can be expected to share the toxicity properties of other local anesthetics. In addi- A single enantiomer of levobupivacaine hydrochloride (Chirocaine) chem- tion, myocardial contractility is depressed and peripheral ically described as S-1-butyl-2-piperidylformo-2’,6’-xylidide hydrochlo- ride. Philadelphia, vasodilation occurs, leading to decreased cardiac output Churchill Livingstone, 2002, ﬁgure 13-16, p. However, Ethyl alcohol is commercially available in 1- or 50-ml these isomers also have reportedly lower potency than their ampules as a colorless solution that can be injected readily through small-bore needles. However, speciﬁc gravity is Na channels or action potentials depends on the pattern not of concern when injecting on the peripheral nerve because injection takes place in a nonﬂuid medium. Here the authors have quantitated the stereopoten- usually used undiluted (absolute or 95% concentration). The ﬁrst reported injection of a neurolytic solution occurs chieﬂy in the liver and is initiated principally by 20 alcohol dehydrogenase. Levy and Baudouin (1906) were no pain relief is present in weeks, then the neurolysis is incomplete and needs repetition. It is indicated for patients followed by degeneration and absorption of all the compo- with limited life expectancy and patients who have recur- nents of the nerve except the neurilemma. Potential trations of alcohol, there is consensus regarding maximum side effects of neurolytic agents include neuritis and deaf- and minimum concentrations. For complete paralysis, the ferentation pain, motor deﬁcit when mixed nerves are concentration must be stronger than 95%. From Labat and ablated, and unintentional damage to nontargeted tis- Greene,30 it may be concluded that a minimum concentra- sue. Histopathologic studies have shown that alcohol extracts ■ Document that the pain will not be relieved by cholesterol, phospholipids, and cerebrosides from the less invasive therapies. A sub- arachnoid injection of absolute alcohol causes similar changes in the rootlets. Histopatho- logically, Wallerian degeneration is evident in the sympa- thetic chain ﬁbers. Therefore, the position of the patient must be in the lateral decubitus position with the painful site uppermost. Then, the pa- tient must be rolled anteriorly approximately 45 degrees to place the dorsal (sensory) root uppermost. B, Effect of alcohol on the spinal cord 50 days after Often, 100% alcohol is diluted 1:1 with a local anesthetic direct cord injection. Note the necrosis and degeneration (arrows) 29 following accidental injection of 100% alcohol into the spinal cord. Am J Pathol use of alcohol is the possible occurrence of alcoholic neu- 35:679, 1961, with permission. It has been postulated that alcoholic neuritis is due to incomplete destruction of somatic nerves. This seems plausible, in that neuritis has not been observed following the intraneural injection of a cranial or somatic nerve that withdrawing the needle. This may be due to the close proximity of tively with mild analgesics such as aspirin or with small the sympathetic ganglia to the intercostal nerves. Bon- the period of regeneration, hyperesthesia and intense ica39 determined that 250 mg of tetracaine dissolved in burning pain with occasional sharp, shooting pain occurs. Fortunately, in most instances, these symptoms times with only transient relief of pain, one infusion of tet- subside within a few weeks or a month. In some cases, daily ever, this complication persists for many months, requir- sympathetic blocks have been employed with excellent ing sedation, and in some instances, the performance of a results. Severe cases a local anesthetic during the insertion of the needle, at of alcoholic neuritis that do not respond to these conserva- the site of injection before the alcohol is injected, and on tive methods may require sympathectomy or rhizotomy. Drugs Used in Interventional Techniques 49 De Takats40 reported three such cases in which sympathec- 1933, Nechaev45 reported the use of phenol as a local tomy was required. This was followed in 1936 by Putnam and Another complication associated with alcohol nerve Hampton,46 who used an injection of phenol to perform a block includes hypoesthesia or anesthesia of the dermato- neurolysis of the gasserian ganglion. In 1947, Mandl47 suggested the injection of phenol to The lack of sensation can overshadow the pain relief ob- obtain permanent sympathectomy. Fortunately, this complication is use in 15 patients without complications, suggesting that it rare and recovery is relatively quick. The stronger concentration produced motor dam- form but can be prepared by the hospital pharmacy. Pain sensation was blocked at lower concentrations gram of phenol dissolves in about 15 ml of water (6. It is usually mixed with saline or that 5% phenol in either Ringer’s solution or oil contrast glycerin. It may be mixed with sterile water or material medium produced selective block of the smaller nerve ﬁ- used for contrast radiography. When mixed with glycerin, slower conduction rates, the C afferents carrying slow it is so viscid that even when warmed, injection must be pain, the Aδ afferents carrying fast pain, and the Aγ con- through at least a 20-gauge needle. It has an advantage over experiments and conﬁrmed the nonselectivity of damage by alcohol in that it causes minimal discomfort on injection. Doppler was the ﬁrst to use phenol to deliberately At concentrations less than 5%, phenol produces pro- destroy nervous tissue in 1925. Concentrations greater than 5% cause man ovarian vessels, he noted downstream vasodilation protein coagulation and nonspeciﬁc segmental demyelin- and ﬂush. Later, he reported treating peripheral vascular ation and orthograde degeneration (i.
Changes in transmembrane potential determine ion flux through voltage-gated channels caverta 100 mg with mastercard erectile dysfunction doctor chicago, not only through the voltage dependence of the electrochemical driving force on the permeant ion order 100 mg caverta visa impotence remedy, but also through the voltage dependence of channel activation discount 100 mg caverta with visa erectile dysfunction evaluation. The fraction of time that a channel is open and allows ionic + + flux is determined by the membrane voltage. Activation of cardiac Na channels or voltage-dependent K channels (see later discussions) increases with membrane depolarization. Rather, the dependence of channel activation on membrane potential is a continuous function of voltage and follows a sigmoidal curve (Fig. The inactivation or availability curve describes the voltage dependence of the occupancy of the inactivated state, and channels may transition to the inactivated state by way of the open or the rested, closed state. Generally, an inactivated channel must first return to the closed state in order to be available to open again. The position of the activation gate changes with the transition from closed to open, and the transition to the inactivated state is determined by the position of the inactivation gate. C, Single-channel current recordings showing the opening of sodium (Na) channels in response to a step change in voltage. The middle tracing reflects the activity of two channels, each with a single-channel amplitude of 1. If membrane depolarization persists, the channel remains inactivated and cannot reopen. This steady-state inactivation increases with membrane depolarization in a sigmoidal fashion (see Fig. Inactivation curves of the various voltage-gated ion channels in the heart differ in their slopes and midpoints of inactivation. For example, sustained membrane depolarization to −50 mV (as may occur in acutely ischemic myocardium) causes + 2+ almost complete inactivation of the fast voltage-gated Na channel, whereas the L-type Ca channel (see 2+ Voltage-Gated Ca Channels) exhibits only little inactivation at this membrane potential. Activation and inactivation curves can overlap, in which case a steady-state or noninactivating current flows. The + existence of such a “window” current has been verified for both the voltage-gated Na and the L-type 2+ 2+ + Ca currents. Channels recover from inactivation and then enter the closed state, from which they can be reactivated and open again (see Fig. Rates of recovery from inactivation vary among the different types of voltage-dependent channels and usually follow monoexponential or multiexponential time courses, with the longest time constants ranging from a few milliseconds, for example, as for the fast sodium current, to + several seconds, as for some subtypes of K currents. Together, the activity of voltage-dependent ion channels in cardiomyocytes over the course of an action potential is tightly regulated by the orchestrated interplay of a number of time- and voltage-dependent gating mechanisms, including activation, inactivation, and recovery from inactivation. The whole-cell current amplitude I is the product of the number of functional channels in the membrane available for opening (N), the probability that a channel will open (P ), and the single-channel currento amplitude (i), or I = N • P • i. Modulation of current amplitudes in single cardiomyocytes thereforeo results from alterations in N, P , i, or any combination of these factors. Changes in the number ofo available channels in the cell membrane may result from alterations in the expression of ion channel– encoding genes. The magnitude of the single-channel current amplitude is dependent, among other factors, on the ionic concentration gradient across the membrane. Phases of the Cardiac Action Potential The cardiac transmembrane action potential consists of five phases: phase 0, upstroke or rapid depolarization; phase 1, early rapid repolarization; phase 2, plateau; phase 3, final rapid repolarization; and phase 4, resting membrane potential and diastolic depolarization (Fig. These phases are the result of passive ion fluxes moving down their electrochemical gradients established by active ion pumps and exchange mechanisms. Above and below are the various channels and pumps that contribute the currents underlying the electrical events. Where possible, the approximate time courses of the currents associated with the channels or pumps are shown symbolically, without trying to represent their magnitudes relative to each other. Although it is likely that other ionic current mechanisms exist, they are not shown here because their roles in electrogenesis are not sufficiently well defined. Upper row, Shown are a cell (circle), two microelectrodes, and stages during impalement of the cell and its activation and recovery. Both microelectrodes are extracellular (A), and no difference in potential exists between them (0 potential). The environment inside the cell is negative, and the outside is positive, because the cell is polarized. One microelectrode has pierced the cell membrane (B) to record the intracellular resting membrane potential, which is −90 mV with respect to the outside of the cell. The cell has depolarized (C), and the upstroke of the action potential is recorded. At its peak voltage, the inside of the cell is approximately +30 mV with respect to the outside of the cell. The repolarization phase (D) is shown, with the membrane returning to its former resting potential (E). Ionic fluxes regulate membrane potential in cardiac myocytes in the following fashion. When only one type of ion channel opens, assuming that this channel is perfectly selective for that ion, the membrane potential of the entire cell would equal the Nernst potential of the permeant ion. By solving the Nernst equation for the four major ions across the plasma membrane, the following equilibrium potentials are obtained: sodium, +60 mV; potassium, −94 mV; calcium, +129 mV; and chloride, −83 to −36 mV (Table + + 34. Therefore, if K -selective channels open, such as the inwardly rectifying K (Kir) channel (see + later), the membrane potential approaches E (−94 mV). When two orK more types of ion channels open simultaneously, each channel moves the membrane potential to the equilibrium potential of their respective permeant ions. The contribution of each ion type to the overall membrane potential at any given moment is determined by the instantaneous permeability of the plasma membrane to that ion. For example, deviation of the measured resting membrane potential from E (K see Table 34. With several permeant ion types, V is a weighted mean of all the Nernst potentials. The intracellular potential during electrical quiescence in diastole is −50 to −95 mV, depending on the type of cell (Table 34. Therefore the inside of the cell is 50 to 95 mV negative relative to the outside + + − of the cell because of the transmembrane gradients of ions such as K , Na , and Cl. Calcium does not contribute 2+ directly to the resting membrane potential, but changes in intracellular free calcium concentration [Ca ]i can affect other membrane conductance values. Ca and thereby lead to spontaneous transient inward currents and concomitant 2+ + 2+ membrane depolarization. This + 2+ protein exchanges three Na ions for one Ca ion and thus generates a current; the direction depends on + 2+ the [Na ] and [Ca ] on the two sides of the membrane and the transmembrane potential difference (see 2+ Electrogenic Transporters). Another transporter, the Na-K pump, electrogenically pumps Na out of the cell and + + + simultaneously pumps K into the cell (three Na outward and two K inward) against their respective + + chemical gradients, keeping the intracellular K concentration high and the intracellular Na + + concentration low. The rate of Na -K pumping to maintain the same ionic gradients must increase as the + + heart rate increases because the cell gains a small amount of Na and loses a small amount of K with + + each depolarization.