Jacob Fuchs

Lovastatin Therapy in Hypercholesterolemia: Effect on Fibrinogen, Hemorrheologic Parameters, Platelet Activity, and Red Blood Cell Morphology

The effect of lovastatin therapy on blood rheology was investigated in 26 hypercholesterolemia patients. Treatment with lovastatin was associated with a significant improvement in whole blood filtration time and a tendency toward normalization in red blood cell morphology. A significant increase was observed in fibrinogen level, in ADP‐induced platelet aggregation, in the percentage of “big” platelets, and in platelet count. The viscosity of whole blood and plasma and the percentage of aggregated platelets did not change significantly. The cause for these hemorrheologic changes and their role in influencing the coronary risk of lovastatin‐treated hypercholesterolemia patients should be further investigated.

Plasma viscosity in ischemic heart disease

Plasma viscosity was measured by the capillary method in 108 patients with ischemic heart disease. The highest value of plasma viscosity was found in 11 patients with severe unstable angina (1.66 +/- 0.068), while in 18 patients with less severe unstable angina plasma viscosity was lower (1.61 +/- 0.056; p less than 0.025). In 43 patients with acute myocardial infarction plasma viscosity was 1.53 +/- 0.10, significantly lower than in the two groups with unstable angina (p less than 0.005). In 36 patients with stable angina plasma viscosity was 1.42 +/- 0.089, similar to that found in 100 normal subjects. Plasma viscosity did not increase in 30 ischemic heart disease patients during exercise-induced myocardial ischemia. It is suggested that the elevated plasma viscosity in unstable angina demonstrated in this study compromises the oxygen delivery to the myocardium and coronary blood flow and therefore may possibly be a factor in the pathophysiology of this syndrome.

Multiform accelerated idioventricular rhythm in acute myocardial infarction: Electrocardiographic characteristics and response to verapamil

Thirteen patients with acute myocardial infarction with multiform accelerated idioventricular rhythm (AIVR) occurring during the first 12 hours of monitoring in the coronary care unit are described. This arrhythmia, similar to the more common uniform AIVR, was intermittent, did not cause hemodynamic compromise, and was not related to more serious ventricular arrhythmias. There was no correlation between the bundle branch block pattern of the multiform AIVR and the electrocardiographic location of the myocardial infarction, but there was a perfect correlation between the frontal plane electrical axis of the multiform AIVR and the electrocardiographic location of the myocardial infarction. The presence of fusion beats between the different forms of AIVR suggests multifocality rather than multiformity. Intravenous verapamil (3 to 5 mg bolus) was administered to 6 patients with multiform AIVR in whom the arrhythmias were persistent enough to allow the evaluation of the effect of verapamil on the arrhythmia. Verapamil caused no change in the rate of AIVR in 1 patient, but in a second patient it decreased the rate by 20 beats/min. In 4 patients, verapamil abolished the arrhythmia: in 2 patients carotid sinus pressure (induced sinus slowing) allowed the emergence of the AIVR at a lower rate, and in the remaining 2 patients the arrhythmia was not observed.

Circulating Aggregated Platelets in Coronary Artery Disease

Circulating aggregated platelets were assessed in 30 patients with stable angina, 22 with unstable angina and 50 with acute myocardial infarction (AMI). Fifty healthy volunteers and 20 noncardiac patients served as controls. One milliliter of venous blood was separated into 2 solutions: 1 composed of ethylenediamine tetraacetic acid (EDTA) and formalin containing reversible and aggregates and 1 composed of EDTA alone containing irreversible aggregates only. By direct microscopic readings the percentage of platelets forming aggregates/1,000 counted platelets was determined in the 2 solutions. The number of reversibly aggregated platelets was estimated by subtracting the percentage of aggregated platelets in the second solution from that in the first solution. In patients with stable angina the percentage of aggregated platelets was higher than in control subjects (15 +/- 4% vs 7 +/- 2%, p less than 0.001). Most aggregated platelets (72% and 76%, respectively) were irreversibly aggregated. In the unstable angina group the percentage of aggregated platelets was similar to that of the AMI group (24 +/- 13% and 24 +/- 10%) and significantly higher than in the stable angina group. Only 11% and 17% of aggregated platelets in patients with stable angina and AMI were irreversibly aggregated and 89% and 83% of them were reversibly aggregated. Participation of platelets in the pathogenesis of unstable angina and AMI may be related to the early reversible phase of platelet activation.

Lovastatin therapy in heterozygous familial hypercholesterolaemic patients: effect on blood rheology and fibrinogen levels

Abstract. Thirteen heterozygous familial hypercholesterolaemic patients were treated with lovastatin for 1 year, and were investigated for the effect on lipid profile, blood rheology and fibrinogen levels. A significant dose‐dependent reduction in serum levels of total and LDL‐cholesterol, Apo B and the ratio of total cholesterol to HDL‐cholesterol was noted. Improvement in red blood cell filterability and an increase in fibrinogen levels were also observed. We conclude that the hypocholesterolaemic effect of lovastatin in familial hypercholesterolaemia is accompanied by changes in blood rheology. While some of these haemorheological changes may be considered beneficial, others may be regarded as unfavourable. The net effect of lovastatin therapy on the coronary risk of familial hypercholesterolaemic patients warrants further investigation.

Pregnancy in a homozygous familial hypercholesterolemic patient treated with long-term plasma exchange

We describe the first pregnancy in a homozygous familial hypercholesterolemic woman who started plasma exchange therapy 3 years before she became pregnant. We especially studied the effects of plasma exchange on lipid profile, uteroplacental circulation, and pregnancy course.

Acute Transmural Myocardial Infarction in Elderly Patients Hospitalized in the Coronary Care Unit Versus the General Medical Ward

The hospital records of 126 patients over 75 years of age with transmural myocardial infarction initially treated in the coronary care unit were compared with a concurrent similar group of 94 patients admitted directly to the general medical wards. The in‐hospital mortality rate for both groups together was 40%. The mortality rate within the coronary care unit was 24% as compared with 46% in the ward group (P < 0.005). However, the mortality rate for the coronary care unit group as a whole (including those patients later transferred to the general ward) was 35 versus 46% in the ward group. Congestive heart failure and cardiogenic shock were the most frequent complications in both groups (47 and 30%, respectively), and they were the main cause of death. Patients with these complications were less likely to be successfully resuscitated, even in the coronary care unit. The overall incidence of serious ventricular arrhythmias and complete heart block was similar to that reported for younger patients. Eleven patients in the coronary care unit group were successfully resuscitated from these arrhythmias and eight survived to be discharged from hospital. In contrast, only two patients in the ward group were successfully resuscitated and eight (9%) patients died suddenly and the fatal event could not be diagnosed. We concluded that elderly patients with an acute myocardial infarction can benefit from early admission to a coronary care unit. J Am Geriatr Soc 35:915–919, 1987

Circulating Platelet Aggregate Size in Ischemic Heart Disease

Platelet aggregate size was measured in 178 patients with ischemic heart disease, among whom 56 had stable angina, 42 suffered from unstable angina, and 80 had had uncomplicated acute myocardial infarction. A group of 50 healthy volunteers and 20 hospitalized noncardiac patients served as controls. Venous blood (0.5 cc) was introduced into a solution containing 11.7 mM EDTA and 1.0 g formaldehyde. Platelet aggregate size was determined by microscopic reading as the number of platelets forming aggregates (per 1000 counted platelets) divided by the number of aggregates. Mean aggregate size was found not significantly different in both control groups, as well as in patients with stable angina and acute myocardial infarction (2.21±0.36 platelets, 2.20±0.58 platelets, 2.28±0.19 platelets, 2.76±1.07 platelets, respectively, p=NS). The highest value was found in the unstable angina group: 4.00±1.40 platelets (p < 0.001 vs other studied groups). Platelet aggregate size was found not to be related to sex, age, medication, or coronary risk factors. Unstable angina may thus be a unique entity in ischemic heart disease concerning its platelet behavior, demonstrated in this study by the increased size of peripheral platelet aggregates, which may have pathogenetic, diagnostic, and eventual therapeutic implications.

Effect of the Beta-Adrenergic Blocker Pindolol on Platelet Function in Chronic Hypertensive Pregnancy

Objective: To evaluate the effects of the beta-adrenergic blocker pindolol on platelet function and pregnancy outcome in chronic hypertensive patients.Methods: A placebo-controlled, prospective, randomized trial in 30 pregnant patients diagnosed as having chronic hypertension. Platelet aggregation and adenosine triphosphate (ATP) release were studied prior to and 7-10 days after pindolol treatment, and in the postpuerperal period.Main Outcome Measure: A difference between the pindolol and placebo groups in platelet aggregation or release of ATP after in vitro exposure to adenosinediphosphate (ADP).Results: No significant difference was demonstrated between the treatment and placebo groups in platelet aggregation or release of ATP after their in vitro exposure to ADP, epinephrine, or both. No significant ameliorating effect of the treatment on perinatal outcome was observed, although maternal diastolic blood pressure was better controlled in the pindolol-treated patients. The known effect of pregnancy in r...

Room temperature ADP induced first stage hyperaggregation of human blood platelets: a previously undescribed phenomenon and its relationship to spontaneous cold induced platelet aggregation

ADP induced human platelet aggregation was shown to be accentuated when tested at 20‐30°C as increased sensitivity and as a greater change of optical density although second stage aggregation and the release reaction did not occur. This previously undescribed phenomenon is defined as room temperature ADP induced first stage hyperaggregation. Aggregation, which occurs under the above mentioned conditions with a quantity of ADP insufficient to maintain the aggregation (usually less than 1 5 μm), is reversible when the temperature is raised to 3 7°C. After rewarming to these temperatures, second stage aggregation appeared in the presence of larger quantities of ADP (usually more than 2 μm) and could be blocked by aspirin. The absence of the release reaction was demonstrated with a lumi‐aggregometer. Spontaneous cold induced platelet aggregation seen after chilling platelets to 0‐4°C is shown to be a distinct phenomenon.