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Biomedical subjects

M Rabinov

Publications and source records attributed to M Rabinov.

35 records · Page 2Linked to original sources
PubMed1991

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.

Administration, Oral↗
PubMed1991

Adverse effects of low-pressure reperfusion after hypothermic cardioplegia in normal and hypertrophic hearts.

The aim of this study was to determine the effect of low-pressure and high-pressure reperfusion, with and without ventricular fibrillation, on the recovery of hypertrophic and normal hearts after hypothermic cardioplegia. Fourteen hearts rendered hypertrophic by valvular aortic stenosis and 18 normal canine hearts were subjected to 1 hour of cardioplegic arrest at 28 degrees C during cardiopulmonary bypass. Each heart was then reperfused at a coronary pressure of either 40 mm Hg (low) or 80 mm Hg (high), initially in the empty beating state and then during ventricular fibrillation. Low-pressure reperfusion produced left ventricular subendocardial ischemia in hypertrophic and in normal hearts, shown by marked depression of subendocardial blood flow, myocardial pH, and myocardial oxygen consumption. In hypertrophic hearts the ischemia was more severe and resulted in a persistent depression of left ventricular function and myocardial oxygen consumption even when coronary pressure was returned to normal levels. High-pressure reperfusion was associated with rapid and complete recovery of myocardial metabolism and function in hypertrophic and in normal hearts. During low-pressure reperfusion, ventricular fibrillation exacerbated ischemia in hypertrophic and in normal hearts. During high-pressure reperfusion, a short period of ventricular fibrillation produced no adverse effects either in hypertrophic or in normal hearts. We conclude that low-pressure reperfusion produces subendocardial ischemia in normal and in hypertrophic hearts even in the empty beating state; in hypertrophic hearts it also impairs recovery of myocardial metabolism and function. The adverse effects of low-pressure reperfusion are exacerbated by ventricular fibrillation.

Animals↗
PubMed1990

Urinary albumin excretion in the healthy population.

In the present study reference values for the albumin excretion rate (AER) and the albumin/creatinine ratio (A/C) in overnight 8-h urine collections (n = 73, group 1) and in 24-h urine collections (n = 25, group 2) were obtained from healthy, nondiabetic, normotensive volunteers. Furthermore, we examined the relationship of these values to age, sex and ethnic group. Albumin was determined by RIA. The mean (+/- SD) values obtained for AER and A/C in overnight urine collections were 6.5 +/- 3.8 mg/24 h and 6.7 +/- 3.6 micrograms/mg creatinine, respectively. These values were significantly lower (P less than 0.001) than the values obtained in 24-h urine collections (AER 11.6 +/- 4.7 mg/24 h and A/C 10.9 +/- 5.0 micrograms/mg creatinine). No difference in AER was observed when the subjects were divided into 10-year age-groups. AER in males was similar to that in females, and AER in European subjects was not different from values obtained for subjects of Oriental (Middle Eastern or North African) origin. Freezing urine specimens resulted in a 25% decrease in AER values. We recommend using freshly obtained 8-h or 24-h urine collections, and considering the excretion of 14 mg/24 h (10 micrograms/min) or 21 mg/24 h (15 micrograms/min), respectively, as the upper limit of normoalbuminuria.

Adult↗
PubMed1989

Comparison of the metabolic response of the hypertrophic and the normal heart to hypothermic cardioplegia. The effect of temperature.

The aim of this study was to test for metabolic differences in the response of hypertrophic and normal hearts to hypothermic cardioplegia. Hypertrophic dog hearts and normal control hearts were subjected to 6 hours of hypothermic cardioplegia with the St. Thomas' Hospital solution. Levels before arrest of subepicardial and subendocardial adenosine triphosphate, creatine phosphate, and lactate in eight hypertrophic hearts were the same as those levels in 12 normal hearts. In hypertrophic hearts, but not in normal hearts, the induction of arrest was slow and was associated with an 11% increase in adenosine triphosphate levels, a 59% decrease in creatine phosphate levels, and a 12-fold increase in lactate levels. Seven hypertrophic hearts and eight normal hearts were studied during 6 hours of arrest and showed no further differences in metabolic response. Reducing the myocardial temperature from 20 degrees C to 12 degrees C slowed the rate of depletion of adenosine triphosphate and the rate of accumulation of lactate in both groups. We conclude that in the nonfailing, severely hypertrophic heart, levels before arrest of high-energy phosphates and lactate are normal, but that marked biochemical changes may occur if the induction of arrest is prolonged because of underdosing with cardioplegic solution. Cooling from 20 degrees C to 12 degrees C improves myocardial preservation in both hypertrophic and normal hearts.

Adenosine Triphosphate↗
PubMed1989

Sensitivity of the recently infarcted heart to cardioplegic arrest. Beneficial effect of pretreatment with orotic acid.

The mortality and morbidity of cardiac operations are increased in the presence of an established, recent myocardial infarct. To help understand the mechanisms for this and to develop a therapeutic strategy, we studied the response of the recently infarcted canine heart to hypothermic cardioplegia and the effect of pretreatment with orotic acid. Orotic acid is a precursor of nucleic acids with the ability to enhance protein synthesis. In 21 greyhound dogs, a myocardial infarct was produced by ligation of the left anterior descending coronary artery. Ten of these then received oral orotic acid (100 mg/kg/day) for 4 days and 11 were untreated. A sham group of eight dogs had a thoracotomy only and therefore had normal hearts (normal group). Four days later, all dogs underwent 60 minutes of cardioplegic arrest at 28 degrees C. Before arrest, stroke work index was lower and myocardial oxygen consumption at comparable work levels was higher in both the orotic acid and untreated infarct groups than in the normal group. After arrest and reperfusion, there was a severe depression of ventricular function in the untreated infarct group, with only 18% recovery of prearrest stroke work. In the orotic acid infarct group, recovery of prearrest function (43%) was similar to that in the normal group (56%) and significantly greater than in the untreated infarct group (p less than 0.01). After reperfusion, the untreated infarct group had a lower oxygen consumption, lower myocardial levels of adenosine triphosphate and glycogen, and higher lactate and water contents than before arrest (all p less than 0.05). In the orotic acid and normal groups, these variables returned to prearrest levels. We conclude that an established, recent myocardial infarct places the noninfarcted myocardium under stress and increases its sensitivity to hypothermic cardioplegia. This sensitivity is markedly reduced by treatment with orotic acid.

Animals↗
PubMed1988

Albumin determination in frozen urines--underestimated results.

Albumin determination by radioimmunoassay in fresh and frozen urine collections from 73 patients were performed. The values for albumin in fresh urines were 1-200 mg/24 h and were significantly higher (p less than 0.001) than the corresponding values in urines frozen for seven days (40.7 mg/24 h +/- 5.0 vs. 32.0 mg/24 h +/- 4.3). Similar results were obtained for protein determination, using turbidimetry, in urine collections from 45 proteinuric patients. Iodinated human albumin added to urine specimens was higher (p less than 0.001) in the pellets from frozen urines compared to urines kept at 4 degrees C for 1 and/or 7 days. By contrast, the radioactivity in the pellet of fresh urines kept at 4 degrees C for 1 or 7 days did not show any significant change. We suggest that freezing results in a partial albumin and protein sedimentation. Thus, determination of albumin in frozen urine specimens underestimates the real value by about 20%. This underestimation will limit our ability to diagnose borderline cases of microalbuminuria.

Albuminuria↗
PubMed1987

Coronary blood flow and myocardial metabolism during reperfusion after hypothermic cardioplegia in the dog.

There have been many studies of reperfusion injury after normothermic ischemia. However, there have been few clinically relevant studies on the nature and time course of recovery of the myocardium during reperfusion after hypothermic cardioplegia. We studied reperfusion in the isolated dog heart supported by another dog. After 2 h of cardioplegic arrest at 20 degrees C, 11 normal hearts were reperfused for 30 min at optimal coronary pressures (60-100 mm Hg mean). The following events occurred: rapid rewarming, a transient hyperemia followed by a rapid return of both coronary blood flow and myocardial oxygen consumption to normal, washout of lactate, recovery of contractility and a slight decline in ATP. Most of these events occurred during the first 15 min of reperfusion. We concluded that, in normal hearts which are well protected during hypothermic cardioplegia, reperfusion at optimal coronary pressure results in recovery of the myocardium within 15 min, with the exception of recovery of ATP levels.

Animals↗
PubMed1987

A double-blind comparison of the relative efficacy, side effects and cost of buprenorphine and morphine in patients after cardiac surgery.

The analgesic efficacy, side effects and cost of administration of regimens of intravenous buprenorphine and intravenous morphine were compared in a randomized double-blind trial performed during the first 24 h after cardiac surgery. Seven patients received buprenorphine by intermittent intravenous injection and six received morphine by continuous infusion. Both these regimens provided good analgesia for the entire 24 h period, with only mild pain at rest and moderate pain on vigorous coughing. Both regimens also produced mild respiratory depression but this was not of clinical importance: the mean arterial PCO2 in both groups was less than 45 mmHg after extubation. The major difference between drugs in the clinical setting was the ease of administration. Buprenorphine had no narcotic code restriction and could be given by intermittent intravenous injection, whereas morphine required checking and handling as a restricted drug and administration by continuous intravenous infusion. When labour and material costs were computed, over the first 24 postoperative hours, it cost $19.76 per patient to administer morphine, but only $3.16 to administer buprenorphine. Thus the use of buprenorphine injections for the first 24 h after cardiac surgery produced pain relief and respiratory depression comparable to that produced by a morphine infusion, but with a significant cost saving in terms of labour and materials.

Buprenorphine↗
PubMed1986

A closed loop microprocessor controller for treatment of hypertension after cardiac surgery.

Hypertension after cardiac surgery is common and requires accurate control by carefully regulated infusions of drugs such as sodium nitroprusside. A microprocessor-based controller has been designed to close the loop between the blood pressure response and the infusion rate of a hypotensive drug. This system has been refined by computer simulation of the blood pressure response to sodium nitroprusside and by experience gained in using the controller in eleven patients in the early recovery period after cardiac surgery. The controller was able automatically to maintain blood pressure within 10% of a specified value. Provision of sophisticated safety features in automatic drug infusion controllers is essential for patient protection.

Cardiac Surgical Procedures↗
PubMed1986

The relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia.

The aim of this study was to document the relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia. Isolated canine hearts perfused by a support dog were subjected to 2 hours of cardioplegia at 20 degrees C. Three hearts were reperfused at each of the following pressures: 20, 40, 60, 80, 100, and 150 mm Hg. The reperfusion period lasted 30 minutes, with the pressure being raised gradually from zero to the test level over the first 2 minutes, then being held constant until the end of the period. The results showed that the normal dog heart after 2 hours of hypothermic cardioplegia is tolerant to a wide range of coronary pressures during reperfusion. Hearts reperfused at pressures between 40 and 100 mm Hg had similar values for coronary blood flow, coronary sinus oxygen saturation, myocardial oxygen consumption, lactate flux, contractility, and myocardial adenosine triphosphate content. If coronary reperfusion pressure was 20 mm Hg, [corrected] myocardial rewarming was delayed, myocardial oxygen consumption was decreased, and myocardial ischemia was manifested by marked lactate efflux, high myocardial lactate concentration, and depletion of adenosine triphosphate. If pressure was 150 mm Hg, coronary flow was excessive. To place these results in the context of coronary artery disease, we measured reperfusion pressure in coronary arteries distal to a stenosis in 10 patients studied at the time of coronary bypass grafting. In 13 arteries with major stenoses, distal mean coronary pressure averaged 31 mm Hg while the simultaneously measured mean aortic or radial artery pressure averaged 66 mm Hg. Thus the average gradient across the stenoses was 35 mm Hg (range 15 to 60 mm Hg). We concluded that in normal hearts without ischemic damage, reperfusion can be conducted satisfactorily at mean coronary pressures from 40 to 100 mm Hg. In setting the tolerable limits for reperfusion pressure in patients with severe coronary artery disease, one should make allowance for pressure gradients of up to 60 mm Hg between the aorta and the distal coronary artery.

Adenosine Triphosphate↗
PubMed1980

Elevation of serum potassium during beta blockade: absence of relationship to the renin-aldosterone system.

Eighteen patients with essential hypertension were treated in a single-blind, crossover study with pindolol and with propranolol. The two drugs were compared because of known differences between them on renin secretion. We noted that plasma renin activity and plasma aldosterone concentration were suppressed by propranolol but not by pindolol. Blood pressure was reduced about equally by both drugs. Serum potassium levels rose in 17 patients on pindolol (p < 0.001) and in 14 patients on propranolol (p = 0.08). Our data suggest that serum potassium elevations induced by beta blockade do not depend on the renin-angiotensin-aldosterone system. Alternative possibilities are discussed.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Successful long-term outcome with prolonged ischemic time cardiac allografts.

BACKGROUND: The limited availability of cardiac allografts together with the increasing number of patients on the waiting list restricts treatment of this population with heart transplantation. An increase in the available donor pool has been facilitated by the use of allografts with prolonged ischemic time (> 240 minutes). METHODS: Short- and long-term outcomes were compared in 150 heart transplant recipients on the basis of allograft ischemic time (< 241 minutes, 241 to 300 minutes, and > 300 minutes). RESULTS: No difference was found in allograft functional capacity, the development of transplant-associated coronary disease, or actuarial survival in the short and long term. CONCLUSIONS: Improved population treatment with prolonged ischemic time cardiac allografts can be safely undertaken without long-term risk to heart transplant recipients.

Adolescent↗