Bunyad Haider

Evidence for Cardiomyopathy in Familial Diabetes Mellitus

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.

Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-(14)C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced (14)CO(2) production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [(14)C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.

Progression of myocardial abnormalities in experimental alcoholism

Abstract To determine those characteristics of left ventricular functional and metabolic alterations in chronic ethanolism that may be time-dependent, up to 36 percent of total daily calories as ethanol was fed to dogs for an average of 18 months (study group 1) or 52 months (study group 2). The short- and long-term study groups were fed the same diet with vitamin supplements and were compared with simultaneously studied control animals. Left ventricular function was assessed in the intact anesthetized dogs using the thermodilution method for end-diastolic volume and stroke volume determinations. During preload increments with saline solution, a significantly greater increase in end-diastolic pressure was observed in both groups receiving ethanol as compared with the control animals; this increase was associated with reduced end-diastolic and stroke volume. However, the responses were similar in the short- and long-term study groups. Increased left ventricular collagen was the apparent basis for the compliance abnormality, but neither variable differed in the groups receiving ethanol. In contrast, the first derivative of ventricular pressure (dP/dt) normalized for preload and afterload, an index of left ventricular contractility, and the velocity of the contractile element (Vce) were significantly reduced only in the long-term study group while tissue calcium was normal. When chromium-51-EDTA was used as an extracellular marker, accumulation of water and sodium in myocardial cells was observed only in the long-term study group, without a reduction of cell potassium. In view of the dilatation of sarcoplasmic reticulum observed on electron microscopy, It is postulated that distortion of the tubular membranes may limit the rate of calcium availability to contractile protein and thus diminish contractile function in chronic alcoholism.

Myocardial infarction postpartum in patients taking bromocriptine for the prevention of breast engorgement

Three cases of myocardial infarction (MI) in women taking bromocriptine for milk suppression are presented. The incidents occurred in 1993 and 1994, the last only two weeks before the withdrawal of the drug from the American market as a drug suitable for ablactation. In one patient, the MI presented on the 12 day postpartum and was accompanied by signs and symptoms reminiscent to ergotism. Another mother suffered MI, accompanied by hypertension, six days after a vaginal delivery complicated by postpartum haemorrhage. The third patient began to take bromocriptine more than 2 weeks postpartum and died suddenly 24 days after her childbirth. To the knowledge of the authors, these are the 12th to 14th literary reports describing an apparent association between the use of bromocriptine for ablactation and the occurrence of MI in the puerperium.

Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition

Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.

Acute eosinophilic myocarditis: Diagnosis and treatment

Abstract Hypereosinophilic syndrome (HES) is a rare disorder of unregulated eosinophilia, which if untreated, may lead to systemic tissue infiltration and inflammation. Cardiac involvement is a common and serious associated complication. We describe a case of HES associated myocarditis mimicking a non-ST elevation MI (NSTEMI). Unlike myocarditis in general, our patient responded well to high dose methylprednisone, the standard of care in HES. We review the clinical presentation, pathophysiology, pathology and treatment of eosinophilic myocarditis related to HES.

Chronic use of aspirin versus indomethacin during non-thrombotic myocardial ischemia: effects on survival.

In view of the reported disparity of the effects upon ischemic myocardium of aspirin and indomethacin, both affecting platelet function and prostaglandin metabolism, we utilized a closedchest canine model to study the effects of chronic treatment with these agents upon arrhythmias, during non-thrombotic coronary occlusion. Group A (N = 20) and Group B (N = 20) were pretreated for seven consecutive days with aspirin 600 mg./day and with indomethacin 25 mg./day, respectively. A group of 36 non-treated animals served as controls. Determination of hemodynamics revealed no significant differences in left ventricular function among the various groups, although blood pressure levels were consistently higher in Group B. Precordial ECG mapping showed lower magnitude of myocardial ischemia in the aspirin group. Changes in water and cation composition of the ischemic tissue after four hours of coronary occlusion were also significantly lower in the aspirin group, suggesting that more extensive tissue swelling in the indomethacin group might have contributed by means of more intensive ischemia, to a higher incidence of ventricular fibrillation. Consistently higher blood pressure levels requiring increased mechanical demands on the myocardium would enhance the negative results observed in the indomethacin group. Mortality rate was 5% for the aspirin group versus 40% and 39% for the indomethacin and the non-treated groups, respectively (P < 0.015). The failure to observe significant platelet accumulation by radioactivity counts in either treated or non-treated animals using 51Cr and 111In-labelled platelet, indicated that microcirculatory thrombosis was not a feature in this model. It is not clear to what extent the reported diverse, mostly inhibitory, effects upon the various enzyme systems and lysosomal membrane ascribed to antiinflammatory agents, are applicable more for indomethacin per se or for the therapeutic schedule used in this study in order to explain its different effect upon ischemic myocardium.

Comparative antiarrhythmic effects of intravenously administered lidocaine and procainamide and orally administered quinidine

Abstract A double-blind control study compared the ventricular antiarrhythmic efficacy of a single dose each of intravenously administered lidocaine and procainamide and orally administered quinidine. A statistically significant reduction in ventricular ectopic contractions occurred immediately and was present 30 minutes and 1 hour after the onset of injection of procainamide. Lidocaine produced a statistically significant reduction in ventricular extrasystoles immediately and for 30 minutes thereafter. No decrease in the incidence of ectopic contractions was observed with either orally administered quinidine or placebo therapy alone. The duration of ventricular antiarrhythmic action of a single injection of procainamide was significantly greater than that of lidocaine. A statistically but probably not clinically significant reduction in systolic blood pressure was observed with procainamide, quinidine and placebo therapy. No change in either systolic or diastolic blood pressure was observed with lidocaine in the dose employed.

Effects of beta-adrenergic inhibition on scar formation after myocardial infarction

In view of clinical interest in the efficacy of beta-adrenergic blockade during acute myocardial infarction (AMI), we have determined the long-term effect of therapy on scar formation after experimental myocardial ischemia. Intact anesthetized dogs underwent acute occlusion of the left anterior descending coronary artery, by means of a balloon catheter, which permitted monitoring of the aortic-peripheral coronary artery pressure gradient during the 4-hour period of balloon inflation. Practolol administration was begun 15 minutes after the onset of ischemia in group A. Control animals (group B) received procainamide to approximate the antiarrhythmic action of beta blockade. Only group A exhibited significant reduction in the ST segments during acute ischemia. Chronic therapy was maintained for 1 month and the mature scar formed in the myocardium was assessed after 4 months. The extent of subendocardial scar was similar in both groups but subepicardial scar formation was significantly less in group A. There was also a significant decrease in the percentage of total myocardium involved with scar in this treatment group. Although thinning of the left ventricular wall was similar for both groups in the central scar region, this process was significantly reduced at the lateral margin in group A. Thus, specific beta-receptor blockade during acute myocardial ischemia and sustained during the repair process can result in a reduced quantity and altered distribution of mature scar.

Ischemic heart failure: Sustained inotropic response to small doses of L-epinephrine without toxicity

As a prelude to a study of severe ischemic heart failure, the therapeutic response of the ischemic ventricle to epinephrine and acetylstrophanthidin in nontoxic doses was determined in 24 intact anesthetized dogs undergoing a first episode of acute regional ischemia. A thrombotic obstruction was produced in the left ventricular dysfunction. The elevation of end-diastolic pressure and reduced stroke volume in control dogs were not significantly altered by administration of strophanthidin. Epinephrine (0.05 mug/kg per min) elicited a significant reduction in end-diastolic pressure and increase in stroke volume. The latter was not attended by an increased incidence of ventricular fibrillation, whereas fibrillation occurred in half of the group given strophantihidin. Thus, the catecholamine was selected to study pump failure. Severe ischemic heart failure was assessed in two groups with scar from previous infarction for up to 4 hours. By 60 minutes of ischemia the increase in end-diastolic pressure and volume and decrease in stroke volume and ejection fraction were comparable in both groups. Thereafter, alternate animals received small doses of epinephrine (0.05 to 0.15 mug/kg per min) with graded increments at 60 minute intervals to counter tachyphylaxis and findings were compared with those in control dogs. Over the subsequent 3 hours, there was progressive deterioration of left anterior descending coronary artery, affecting ventricular function in the untreated group with an increase in end-diastolic pressure from 10 plus or minus 1 to 33 plus or minus 2.4 mm Hg. End-diastolic volume increased by 63 percent; stroke volume and ejection fraction decreased by 48 and 66 percent, respectively. The infusion of epinephrine was attended by a significantly lower end-diastolic pressure of 20 plus or minus 2.5 mm Hg, whereas end-diastolic volume, stroke volume and ejection fraction were restored to control levels after 4 hours of ischemia. Mortality in the untreated group was 62 percent by 4 hours; all seven animals in the treated group survived.