Influence of Proportion of Normal Saline Administered in the Perioperative Period of Renal Transplantation on Kalemia Levels

Background

The hyperchloremic metabolic acidosis triggered by the infusion of normal saline (NS) significantly increases the level of extracellular potassium. In this study we assessed the influence of proportion of NS administered in the perioperative period of renal transplantation on potassium levels in usual clinical practice.

Aprikalim reduces the Na-Ca exchange outward current enhanced by hyperkalemia in rat ventricular myocytes

Bacground. Aprikalim, an adenosine triphosphate (ATP) sensitive K⁺ (K_ATP) channel opener, attenuates the elevation of intracellular Ca²⁺ concentration ([Ca²⁺]_i) and improves the contractile functions after hyperkalemic and hypothermic cardioplegia. There is evidence that cardioplegia increases the Na⁺-Ca²⁺ exchange activity without affecting Ca²⁺ influx through L-type Ca²⁺ channels or Ca²⁺ content in the sarcoplasmic reticulum, the intracellular Ca²⁺ store.Methods. We measured the Na⁺-Ca²⁺ exchange outward current with the patch-clamp technique in single rat ventricular myocytes exposed to hyperkalemia and hypothermia in the presence of aprikalim. The intracellular calcium concentration ([Ca²⁺]_i) during cardioplegia, and the contractile function and [Ca²⁺]_i transients induced by electrical stimulation or caffeine during rewarming and reperfusion in single ventricular myocytes were also determined. Contraction and [Ca²⁺]_i were determined with video tracking and spectrofluorometry, respectively.Results. Aprikalim, 100 μmol/L, the effect of which was blocked by glibamclamide, a K_ATP inhibitor, significantly attenuated the hyperkalemia-elevated Na⁺-Ca²⁺ exchange current by 26% and 11% at 22°C and 4°C, respectively. Aprikalim also attenuated significantly the [Ca²⁺]_i elevated during cardioplegia. Furthermore aprikalim significantly attenuated the reduction in amplitude and prolongation in duration of contraction of myocytes after cardioplegia. The effects of aprikalim mimicked those of nickle (Ni²⁺), a Na⁺-Ca²⁺ exchange blocker. The electrically or caffeine-induced [Ca²⁺]_i transients were unaltered by cardioplegia or aprikalim.Conclusions. Aprikalim attenuates the Na⁺-Ca²⁺ exchange outward current elevated by hyperkalemia, which may attenuate the [Ca²⁺]_i elevation during hyperkalemia and improve the contractile function after cardioplegia in the ventricular myocyte. The study provides further support that addition of a K_ATP channel opener to the cardioplegic solution may produce beneficial effects in open heart surgery.     

Effects of Delay in Administration of Potassium Cardioplegia to the Isolated Rat Heart

Ischemic injury to the heart in the period between aortic cross-clamping and administration of cardioplegic solution was evaluated in the normothermic rat heart model. After isolation and control perfusion with oxygenated Krebs-Henseleit bicarbonate buffer, the hearts were given lactated Ringer's cardioplegic solution (30 mEq of K⁺ per liter) for 2 minutes at three different intervals following aortic clamping: no delay, 2-minute delay, and 5-minute delay. Thereafter, the hearts were left unper-fused and the time to initiation of ischemic contracture was recorded. Adenosine triphosphate (ATP) and creatine phosphate levels were measured in all groups prior to and at the conclusion of cardioplegia administration.A 2-minute delay in the administration of cardioplegic solution resulted in significantly lower (p < 0.001) ATP levels that were restored after 2 minutes of cardioplegia administration. Contracture times were not significantly altered. A 5-minute delay resulted in significantly shorter (p < 0.001) contracture times and significantly lower (p < 0.001) ATP levels that were not restored to preischemic levels by 2 minutes of cardioplegia administration.The fate of the myocardium may be insensitive to events that occur during the earliest moments of ischemia provided that rapid administration of oxygenated potassium cardioplegia follows the ischemic period and restores preischemic high-energy phosphate stores. However, there is a critical ischemic time during the initial interval before cardioplegia that is associated with an impaired ability of the myocardium to tolerate subsequent ischemia.     

Verapamil worsens rate of development and hemodynamic effects of acute hyperkalemia in halothane-anesthetized dogs: effects of calcium therapy

The hemodynamic effects of verapamil pretreatment versus no pretreatment were evaluated in five acutely hyperkalemic dogs. Using ECG evidence for severe hyperkalemia, the halothane-anesthetized dogs were rendered acutely hyperkalemic to similar plasma levels of K+ (K+ = 8.2 +/- 0.8 mEq/l verapamil plus hyperkalemia, K+ = 9.4 +/- 0.2 mEq/l hyperkalemic controls). The verapamil-hyperkalemic group had significantly lower cardiac indexes (CI) (CI = 1.3 +/- 0.5 1 X min-1 X m-2 verapamil plus hyperkalemia vs. CI = 3.0 +/- 0.2 1 X min-1 X m-2 hyperkalemic controls) and lower mean arterial pressures (MAP = 60 +/- 13 mmHg verapamil plus hyperkalemia vs. MAP = 96 +/- 7 mmHg hyperkalemic controls). Calcium therapy for hyperkalemia that returned CI to control levels in hyperkalemic controls only partially reversed the severe hemodynamic depression and did not improve the AV block seen during hyperkalemia in the presence of the calcium entry blocker verapamil. Surprisingly, the total mEq of KCl infused at the same rate into verapamil-pretreated dogs to result in similar high serum potassium levels was only one-third that required in dogs not pretreated with verapamil (1.6 +/- 0.3 mEq/kg KCl in verapamil-hyperkalemia group vs. 5.0 +/- 0.7 mEq/kg KCl in hyperkalemic controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrolyte versus Blood Cardioplegia: Randomized Clinical and Myocardial Ultrastructural Study

In 40 consecutive patients undergoing coronary artery bypass, one of two solutions for cardioplegia, each containing 30 mEq/L of K⁺ was used randomly. The groups were comparable except for intramyocardial temperature. With electrolyte solution (Group A), it was 16.5° ± 0.34°C, while with blood from the pump-oxygenator (Group B) it was 20.3° ± 0.41°C (p < 0.001). After bypass left atrial pressure (LAP) was 11.9 ± 0.67 torr in Group A and 8.1 ± 0.49 torr in Group B (p < 0.001). CPK-MB was elevated in 45% of Group A patients versus 15% in Group B (p < 0.05). No patient died. Two myocardial infarctions occurred in Group A and one in Group B. Stereological morphometric electron microscopy was performed on biopsy specimens taken from the left ventricle (1) before perfusion, (2) after cardioplegia, and (3) 30 minutes after reperfusion. Group A showed marked intracellular edema, mitochondrial swelling, pronounced depletion of glycogen stores, and focal myofibrillary disorganization. Group B showed near normal myocardial ultrastructure with increased glycogen stores and minimal mitochondrial swelling. Morphometric analysis revealed a statistically significant increase in the degree of mitochondrial swelling (51%) in Group A compared with Group B after reperfusion (p < 0.001). Thus, blood K⁺ cardioplegia resulted in better preservation of myocardial ultrastructure, lower ventricular filling pressure, and lesser CPK-MB release compared with this particular electrolyte cardioplegia.     

Hyperkalaemia: a complication of warm heart surgery

A case is presented of hyperkalaemia (13.6 mEq · L^?1) occurring during cardiopulmonary bypass using warm blood cardioplegia (K⁺ 40–60 mEq · L^?1). Treatment with epinephrine, calcium chloride, sodium bicarbonate, and furosemide reduced K⁺ to 6.5 mEq · L^?1 within 30 min and myocardial performance was enhanced with amrinone and cardiac rhythm was controlled with A-V segmental pacing. It is believed that the hyperkalaemia resulted from a combination of the surgical procedure (mitral valve replacement) and the use of warm cardioplegia. The purpose of this report is to increase the awareness of the possibility of hyperkalaemia with warm cardioplegia and to describe a successful therapeutic regimen.     

Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports

The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K⁺) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K⁺ during treatment of DH with insulin included the starting serum K⁺ level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.     

Excellent outcomes in a case of complex re-do surgery requiring prolonged cardioplegia using a new cardioprotective approach: adenocaine

A 71-year-old high-risk fourth-time redo male patient was diagnosed with prosthetic valve endocarditis of both aortic and mitral valves, and subsequently required a re-operative aortic and mitral valve replacement. He was placed on cardiopulmonary bypass (CPB) and arrested with normothermic hyperkalemic all-blood cardioplegia (microplegia) containing adjunctive adenosine-lidocaine-magnesium (adenocaine); aerobic arrest was maintained with near-continuous retrograde low potassium (approximately 2 mEq/L) adenocaine microplegia. After 4 hours of arrest on CPB, the aortic valve was found to be incompetent and was resected. A root replacement was required utilizing a Medtronic Freestyle Root prosthesis. Four separate periods of cross-clamp were required during the course of the entire operation. The patient was on CPB for 9.8 hours with a total cross-clamp time of 7 hours, during which he received 72 liters of all-blood adenocaine microplegia. After a terminal "hot shot" with adenocaine microplegia and no added potassium, CPB was discontinued with no systemic hyperkalemia (5.1 mmol/L), no hemodilution (hematocrit, 24%), no balloon pump, no antiarrhythmic agents, and modest inotropic support. The patient was hemodynamically stable, was extubated in 12 hours, and was transferred out of the cardiac ICU after 48 hours with a subsequent uneventful recovery.     

Storage Age of Transfused Red Blood Cells During Liver Transplantation and Its Intraoperative and Postoperative Effects

Background

Recent studies suggest that the storage age of red blood cells (RBCs) may be associated with morbidity and mortality in surgical patients. We studied perioperative effects of RBC storage age in patients undergoing orthotopic liver transplant (OLT).

Methods

Adult patients who received ≥5?U of RBCs during OLT between January 2004 and June 2009 were studied. The subjects were divided into two groups according to the mean storage age of RBCs they received: new or old RBCs (stored ≤14 or >14?days, respectively). Effects of storage age of transfused RBCs during OLT on intraoperative potassium (K⁺) concentrations, incidence of hyperkalemia (K⁺ ≥5.5?mmol/L), postoperative morbidity, and patient and graft survival were studied.

Results

The mean serum K⁺ concentrations and the incidence of hyperkalemia during OLT were significantly associated with storage age of the RBCs. Logistic analysis showed that storage age of RBCs was an independent risk factor for intraoperative hyperkalemia (odds ratios 1.067–1.085, p?<?0.001) in addition to baseline K⁺ concentration and units of RBCs transfused. Patient and graft survival and postoperative morbidity including postoperative ventilation, reoperation, acute renal dysfunction defined by the RIFLE criteria was not associated with old RBCs.

Conclusions

Transfusion of RBCs stored for a longer time was associated with intraoperative hyperkalemia but not with postoperative adverse outcomes in adult OLT. Prevention and treatment of potentially harmful hyperkalemia should be considered when old RBCs are administered.     

Correction of hyperkalemia by bicarbonate despite constant blood pH.

Patients having hyperkalemia often are given bicarbonate to raise blood pH and shift extracellular potassium into cells. Blood pH in many hyperkalemic patients, however, is compensated. To determine whether bicarbonate, independent of its pH action, affects plasma potassium, 14 hyperkalemic patients were treated with bicarbonate in 5% dextrose. In five patients (changed pH group), blood pH rose at least 0.08, while in nine (constant pH group), it changed less than 0.04. In the first group, pH rose 0.12, bicarbonate rose 5.9 mEq/liter, and plasma potassium fell 1.6 mEq/liter, and plasma potassium fell 1.4 mEq/liter. The correlation between changes in plasma potassium and bicarbonate was identical in the two groups and independent of urinary potassium excretion. Four additional patients, who were treated with 5% dextrose alone, did not significantly lower their plasma potassium, although subsequent treatment with bicarbonate in 5% dextrose lowered their plasma potassium. Thus, bicarbonate lowers plasma potassium, independent of its effect on blood pH, and despite a risk of volume overload, should be used to treat hyperkalemia in compensated acid-base disorders, even in the presence of renal failure, provided the plasma bicarbonate concentration is decreased.     

Hyperkalemia in hospitalized patients

Objective: Evaluate the prevalence of hyperkalemia(potassium < 5.5 mmol/l) in hospitalized patientsnot on dialysis, as well as the association ofmedications, impaired renal function and comorbidconditions with hyperkalemia.Design: A retrospective case-control method.Setting: A tertiary care teaching hospital.Patients: Hyperkalemic adults not on dialysis withage and sex matched controls.Interventions: None.Main outcome measures: The use of medicationsassociated with hyperkalemia and renal function usinga calculated creatinine clearance were compared in thehyperkalemic and control groups.Results: 35 adult patients with hyperkalemia who werenot receiving dialysis were identified, with aprevalence in the hospitalized population of 3.3%.The hyperkalemic patients were older than the generalhospital population (p < 0.05). Compared withcontrols, hyperkalemic patients: had a lowercreatinine clearance (p < 0.05), were more likely tobe taking angiotensin-converting enzyme inhibitors (p < 0.05), and had an increased frequency of diabetesmellitus (p < 0.001). All of the control patientssurvived their hospitalization, but the mortality rate in the hyperkalemic group was 17% (p < 0.0001). Noneof the deaths were directly attributable to hyperkalemia.Conclusions: Hyperkalemia is more frequent in olderpatients and is usually mild. Hyperkalemia isassociated with diabetes mellitus, diminished renalfunction and the use of angiotensin-converting enzymeinhibitors. An elevated serum potassium level in ahospitalized patient may be a marker for asignificantly increased risk of death, which is due tounderlying medical problems and is not a consequenceof the hyperkalemia. This revised version was published online in August 2006 with corrections to the Cover Date.     

Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: a unique clinical/physiologic exercise in internal potassium balance

The absence of significant losses of potassium in the urine makes dialysis-associated hyperglycemia (DH) a model for the study of the internal potassium balance. Studies of DH have revealed that hyperkalemia is frequent at presentation, insulin infusion is usually the only treatment required, and the magnitude of the decrease in serum potassium concentration (K⁺) during treatment of DH with insulin depends on the starting serum K⁺ level, the decreases in serum glucose concentration and tonicity, and the increase in serum total carbon dioxide level. We present an analysis of these findings based on previously studied actions of insulin. Calculations of transcellular potassium shifts based on the combined effects of insulin—the increase in the electrical potential differences (hyperpolarization) of the cell membranes and the correction of the hyperglycemic intracellular dehydration through decrease in serum glucose concentration—produced quantitative predictions of the decrease in serum K⁺ similar to the reported changes in serum K⁺ during treatment of DH with insulin. The lessons from analyzing serum K⁺ changes during treatment of DH with insulin are applicable to other conditions where internal potassium balance is called upon to protect serum K⁺, such as the postprandial state. The main questions related to internal potassium balance in DH that await clarification include the structure and function of cell membrane potassium channels, the effect of insulin on these channels, and the mechanisms of feedforward potassium regulation.     

INSULIN AND MINERALOCORTICOIDS INFLUENCE ON EXTRARENAL POTASSIUM METABOLISM IN CHRONIC HEMODIALYSIS PATIENTS

Insulin-mineral corticoids effects on extrarenal K⁺ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K⁺ over the past 12 months: > 6.0 mEq/L (G1, n = 5), = 5.1–6.0 mEq/L (G2, n = 5), ≤5.0 mEq/L (G3, n = 5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO₃^?, glucose, body weight, blood pressure and heart rate were measured before and 60′ after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1–T3); G1 received fluorohydrocortisone (FHC) 0.1 mg–0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 ± 23 to 157 ± 52 mg/dL, P < 0.001) and insulin (11.8 ± 6.2 to 46.8 ± 19.5 μU/mL, P<0.001), with a drop in K⁺ (5.1 ± 0.6 to 4.8 ± 0.7 mEq/L, P= 0.001) and aldosterone (453 ± 373 to 383 ± 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r = ?0.54, P<0.04) to serum K⁺ at T60, in all patients. (B) No major pH, HCO₃ and aldosterone changes were observed in the 3 groups. Despite that, K⁺ dropped in G1 by FHC (6.7 ± 0.9 to 5.9 ± 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 ± 0.4 to 5.4 ± 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 ± 0.2 to 5.8 ± 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K^? by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K⁺ handling in steady state anuric dialysis patients.     

Therapeutic approach to hyperkalemia

The foremost step in the initial clinical management of hyperkalemia is to decide whether a hyperkalemic patient requires immediate treatment to avoid a life-threatening situation (serum potassium concentration >6.0 mEq/l and EKG changes). When the decision for urgent treatment of hyperkalemia is based on EKG changes, an important caveat for clinicians is that absent or atypical EKG changes do not exclude the necessity for immediate intervention. Once an urgent situation has being handled with intravenous push of a 10% calcium salt, the initiation of short-term measures can be launched by either a single or combined regimen of the three agents that cause a transcellular shift of potassium - insulin with glucose, beta(2)-agonist (albuterol), and NaHCO(3). As the first choice among these available options, we favor an intravenous bolus of 10 units of insulin with 50 ml of 50% glucose alone or in combination with 10-20 mg of albuterol by nebulizer. These can be repeated as required until the institution of hemodialysis. The combination of insulin with glucose and NaHCO(3) as an another option needs further clarification for its additive effects. However, NaHCO(3) has lost its favor because of its poor efficacy as a potassium-lowering agent when used alone. The next step is to remove potassium from the body - diuretics (furosemide), cation exchange resin (kayexelate) with sorbitol, and dialysis (preferably hemodialysis). The final important step for the managements of hyperkalemia is a long-term plan to prevent its recurrence or worsening. In addition to every effort to elucidate underlying causes and pathophysiologic mechanisms for hyperkalemia, an extensive search must be made to uncover overt or sometimes covert medications that may have led to the development of hyperkalemia. Furthermore, one must obtain detailed dietary and medical history of hyperkalemic patients.     

Hyperkalemia in chronic peritoneal dialysis patients

Background. Chronic peritoneal dialysis (PD) patients often develop hypokalemia but less commonly hyperkalemia.Methods. We explored incidence and mechanisms of hyperkalemia in 779 serum samples from 33 patients on PD for 1 − 59 months. Normal serum potassium concentration was defined as 3.5 − 5.1 meq/l.Results. Mean monthly serum potassium concentrations were normal (except for 1 month), but we observed hypokalemia (<3.5 meq/l) in 5% and hyperkalemia (>5.1 meq/l) in 14% of 779 serum samples. Incidence of hyperkalemia did not change over time on PD: Year 1 (15%), Year 2 (11%), Year 3 (19%), Years 4–5 (22%). Hyperkalemia was mostly modest but occasionally extreme [5.2–5.4 meq/l (55%), 5.5–5.7 meq/l (21%), 5.8–6.0 meq/l (10%), >6.0 meq/l (14%)]. Of 31 patients (2 excluded due to brief PD time), 39% displayed hyperkalemia only, 23% displayed hypokalemia only, and the remainder (38%) displayed both or neither. Comparing hypokalemia-only with hyperkalemia-only patients, we found no difference in potassium chloride therapy, medications interrupting the renin-angiotensin system, small-molecule transport status, and renal urea clearance. We compared biochemical parameters from the hypokalemic and hyperkalemic serum samples and observed lower bicarbonate concentrations, higher creatinine concentrations, and higher urea nitrogen concentrations in the hyperkalemic samples (p < 0.001 for each), without difference in glucose concentrations.Conclusion. We observed hyperkalemia 3 times as frequently as hypokalemia in our PD population. High-potassium diet, PD noncompliance, increased muscle mass, potassium shifts, and/or the daytime period without PD might contribute to hyperkalemia.     

Aldosterone responsiveness in patients with diabetes mellitus

Plasma aldosterone (PA) and plasma renin activity (PRA) were determined in 44 diabetics, of whom nine were normotensive but not nephropathic (group 1), 10 were hypertensive but not nephropathic (group 2), and 25 were hypertensive and nephropathic (group 3); they were kept in balance on a diet composed of 10 to 20 mEq. of sodium (Na) and 100 mEq. of potassium (K). Supine PA in group 1 was 38 +/- 7 ng. per deciliter, whereas in normals it was 24 +/- 2 ng. per deciliter (P less than 0.05); beyond that, neither supine nor upright PA or PRA differed significantly from normal in groups 1 and 2. By contrast, in group 3, supine PA was 13 +/- 1 ng. per deciliter and PRA 2.0 +/- 0.2 ng./ml. and upright PA was 39 +/- 7 ng. per deciliter and PRA 3.8 +/- 0.5 ng./ml., all significantly lower than those in the other groups (P less than 0.01). Nine patients, one in group 1 and eight in group 3, had low supine and upright PA and PRA; four had hyperkalemia. An additional nine patients in group 3 had low upright PA, with normal or low PRA; two had hyperkalemia. Of the 18 patients with low upright PA, K correlated with glucose (R = 0.46, P less than 0.05). These results suggest (1) the renin-aldosterone system generally responds normally in diabetics without nephropathy but responds subnormally when nephropathy is present, (2) hyporeninemic hypoaldosteronism is frequent in diabetics with nephropathy but may occur in the absence of clinical nephropathy, and (3) hyperkalemia in some diabetic patients may be secondary to hypoaldosteronemia and hyperglycemia.     

Substrate Cardioplegia during Hypothermic Arrest in the Alloxan Diabetic Dog

In an experimental study, 26 mongrel dogs were treated with alloxan (50 mg per kilogram) to induce fasting hyperglycemia and diabetes. The animals were randomly subdivided into two groups, one of which received 100 mg of propranolol in divided doses for two weeks. The animals underwent sternotomy and were placed on total cardiopulmonary bypass. After aortic cross-clamping, each animal received 10 ml per kilogram of cardioplegic solution. Two different solutions were used, a standard hyperkalemic solution and a high-energy glucose-insulin-potassium (GIK) substrate. Baseline studies were made on the four groups of diabetic animals.Animals given potassium cardioplegia but no propranolol showed statistically significant decreases in cardiac index, heart rate, mean arterial pressure, and minute left ventricular stroke work index after bypass. In contrast, animals given GIK cardioplegia but no propranolol showed no changes in any of these measurements. Animals administered propranolol and potassium cardioplegia experienced decrease in mean arterial pressure from 77.5 ± 14.1 mm Hg before bypass to 57.5 ± 17.8 mm Hg after bypass. A similar reduction occurred in animals given propranolol and GIK cardioplegia. However, in this group, the cardiac index increased from 1.78 ± 0.38 L/min/m² before bypass to 2.96 ± 0.73 L/min/m² after bypass (p < .006). Similarly, the minute left ventricular stroke work index increased after bypass in these animals. This study demonstrates the protective effect against myocardial ischemia of the addition of substrate to the cardioplegic solution in diabetic animals subjected to aortic cross-clamping during cardiopulmonary bypass, one group receiving propranolol and one group not receiving it.     

Hypothermic Ischemic Arrest versus Hypothermie Potassium Cardioplegia in Human Beings

To determine if the addition of potassium enhances the myocardial protective effect of intracoronary perfusion hypothermia during aortic cross-clamping, 50 patients undergoing aortocoronary bypass grafting were studied in a randomized, prospective, double-blind fashion. Twenty-six patients received a cold crystalloid solution infused with a handheld syringe into the root of the cross-clamped aorta every 20 minutes, and 24 patients received the same solution but with 25 mEq/L of potassium chloride added, infused in a similar manner. Both groups were analyzed by mortality, rate of perioperative myocardial infarction (electrocardiographic changes, MB-CPK enzyme release, and preoperative and postoperative gated cardiac blood pool scans), intraoperative hemodynamic changes, intraoperative lactate determinations, postoperative arrhythmias, and requirement for pressor or intraaortic balloon pump support.One patient in the potassium cardioplegia group died (massive pulmonary embolism), and none in the hypothermic perfusion group died. Possible perioperative myocardial infarction was diagnosed by more than one marker in 4 of 26 patients in the hypothermic perfusion group and 5 of 24 patients in the potassium group (p = 0.61). There were no differences between the two groups in terms of hemodynamic changes, lactate production, postoperative arrhythmias, or the need for postoperative hemodynamic support.This study in human beings could not demonstrate a specific protective effect of potassium, beyond that afforded by myocardial perfusion hypothermia and wash-out. The data suggest that myocardial hypothermia, achieved through cold intracoronary arterial perfusion, may be the most important beneficial component of so-called cardioplegia for attaining effective intraoperative myocardial preservation in human beings.     

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation.

OBJECTIVE: We have recently shown that adenosine instead of supranormal potassium in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that hyperkalemia has unfavorable effects on vascular endothelial function. Three pathways have been identified as major vasodilatory pathways: the nitric oxide (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves postcardioplegic endothelial function. METHODS: Sixteen pigs were randomized to receive either cold (6 degrees C) hyperkalemic cardioplegia (n=8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n=8). After 1h of cold ischemic arrest, coronary blood flow was monitored for the following 2h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A(2) analog) and then bradykinin-mediated relaxation was investigated. To differentiate between the vasodilatory pathways the relaxation was assessed in the absence and presence of inhibitors of the COX (indomethacin), NO (L-NAME+carboxy-PTIO), and EDHF (apamin+charybdotoxin) pathways. RESULTS: Invivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1h after cross-clamp release (from (ml/min/100 g, mean+/-SD) 50.9+/-13.9 to 72.8+/-21.9, p=0.010). The difference was, however, not statistically significant between groups. Invitro: Maximal relaxation without blockers was 27.4+/-10.1% of maximal tension in the adenosine group and 22.2+/-7.5% in the hyperkalemic group. To investigate EDHF-dependent vasodilation the vessel rings were simultaneously treated with indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic group was then reduced to 47.4+/-17.4% of maximal tension, which was a significant reduction compared to the adenosine group with a maximal relaxation of 20.6+/-8.7% (p=0.028). CONCLUSION: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation.     

Isohydric regulation of plasma potassium by bicarbonate in the rat.

pH and bicarbonate affect many metabolic reactions but each may change independently. To study bicarbonate's effect onplasma potassium, blood bicarbonate in normal, hypokalemic or hyperkalemic rats was either maintained constant, lowered by hydrochloric acid or raised by sodium bicarbonate administraion. Blood pH was maintained constant by changing PCO2. In normokalemia lowering bicarbonate increased plasma potassium 2.0mEq above values obtained in the other groups. To eliminate urinary potassium losses, experiments were also performed in rats with bilateral ureteral ligation. Again, plasma potassium concentration rose significantly more in the lowered bicarbonate group. Similarly, in hypokalemia, plasma potassium rose 1.2 and 0.4mEq in the lowered and unchanged groups, but fell 0.2mEq/liter in the elevated group. Differences could not be ascribed to renal potassium losses as potassium excretion was essentially zero in each group. In hyperkalemia, plasma potassium concentration remained elevated for 150 min in the lowered bicarbonate group but fell 1.3 and 2.0mEq in the unchanged and elevated groups, respectively. Urinary potassium losses in the three groups were statistically identical. In all experiments blood pH was maintained unchanged during the experiment. The data show that bicarbonate, independent of blood pH, alters transcellular potassium distribution suggesting the usefulness of bicarbonate therapy in hyperkalemia even at a compensated blood pH.