Effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium

The effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium were determined in nine adult mongrel dogs susceptible to sustained ventricular tachyarrhythmias. The dogs were studied at 3 to 30 days after two stage occlusion and reperfusion of the mid left anterior descending coronary artery. Unipolar cathodal stimulation (pulse duration 2 ms, drive cycle length 300 ms) was used to evaluate excitability and refractoriness at a total of 19 normal and 22 infarct sites both before and 15 to 30 minutes after intravenous infusion of procainamide, 20 to 25 mg/kg body weight. The electrophysiologic effects of procainamide were evaluated at the time of the plateau phase of procainamide's antiarrhythmic activity in this model. At normal sites, procainamide had only a minimal effect on the mean diastolic excitability threshold (increased from a mean [± standard deviation]of 0.07 ± 0.02 to 0.08 ± 0.02 mA [probability (p) = not significant (NS)], the mean effective refractory period (increased from 137 ± 10 to 139 ± 11 ms [p = NS]) and the mean ventricular refractory period at twice diastolic threshold (increased from 156 ± 12 to 163 ± 16 ms [p <0.01]). At infarct sites, the mean diastolic excitability threshold was similarly unchanged after procainamide (from 0.57 ± 1.13 to 0.57 ± 1.09 mA [p = NS]), but both the mean effective refractory period (from 142 ± 17 to 159 ± 27 ms [p <0.001]) and the mean ventricular refractory period at twice diastolic threshold (from 166 ± 25 to 187 ± 33 ms [p <0.001]) were moderately prolonged. In addition, dispersion of refractoriness between normal and infarct sites as well as within areas of infarcted myocardium was often either unchanged or increased rather than decreased by procainamide.

Thus, the antiarrhythmic activity of procainamide in this canine model of chronic myocardial infarction was not explained by an effect on the excitability or refractoriness of normal myocardium, by changes in the diastolic excitability of infarcted tissue or by an effect on the dispersion of refractoriness. The most prominent effect of procainamide was to decrease the excitability of abnormal myocardium during the relative refractory period and to prolong the refractoriness of abnormal myocardium.     

The hemodynamic consequences of cardiac arrhythmias: Evaluation of the relative roles of abnormal atrioventricular sequencing,irregularity of ventricular rhythm and atrial fibrillation in a canine model

To evaluate the hemodynamic consequences of various cardiac arrhythmias, hemodynamic and angiographic studies were performed on 20 open-chest, atrioventricular (AV) heart-blocked dogs during various programmed pacing protocols. Protocols included AV pacing at intervals of 100 msec and ?100 msec, ventricular (V) pacing during AV dissocation, and V pacing during atrial fibrillation (AF). In addition, the effects of regular versus irregular V pacing were also evaluated. During regular V pacing, cardiac output was optimal at an AV interval of 100 msec, but decreased by 25% at AV ?100 msec and by 18% during both AV dissociation and AF. During irregular V cycles, cardiac output decreased further (e.g., by an additional 7% during AF). Pulmonary venous regurgitation was observed only during AV dissociation and during regular pacing at AV ?100 msec. Notably, mitral valvular regurgitation was observed only during irregular V cycles, but not during regular V pacing, even in the presence of AV dissociation or AF. Using these methods it was possible to resolve some previously reported controversies regarding the relative importance of AV sequencing, atrial systole versus AF, regular versus irregular rhythms, as well as the possible contribution of mitral and/or pulmonary venous regurgitation to the adverse hemodynamics of various cardiac arrhythmias.     

Increased R-wave amplitude induced by acute myocardial ischemia in the dog: A predictor of malignant ventricular arrhythmias

The ability of an increase of 25 % or greater in the sum of R-wave amplitudes in leads X, Y, Z, L₂, and V₅ to predict the occurrence of malignant ventricular arrhythmias (10 or more ventricular premature beats/min, ventricular tachycardia [5 or more consecutive premature beats], and/or fibrillation) was evaluated in 17 dogs during experimental acute myocardial ischemia. Each dog underwent a 15 minute ligation of the left anterior descending coronary artery followed by reperfusion and after recovery, 2 hours later, a 15 minute ligation of the circumflex coronary artery. During ligation of the left anterior descending coronary artery, 12 of 17 dogs (71%) showed no R-wave increase and no arrhythmias (true-negative response). In 5 (29%) of 17 dogs malignant ventricular arrhythmias developed: 2 of 5 (40%) dogs with arrhythmias had a concomitant R-wave increase (true-positive response), and 3 of 5 (60%) with arrhythmias had a less than 25% increase in R-wave amplitude (false-negative results). During circumflex coronary artery ligation, 13 of 17 (76%) dogs showed both R-wave increases and arrhythmias (true-positive response). Four (24%) of 17 dogs had no arrhythmias: 3 of 4 (75%) with no arrhythmias also had a less than 25% increase in R-wave amplitude (true-negative response), whereas 1 of 4 (25%) dogs with no arrhythmias had an increase in R-wave amplitude (false-positive response). In dogs with both arrhythmias and R-wave increases, R-wave changes preceded the onset of arrhythmias by a mean (± standard deviation) of 1 minute 27 seconds (± 43 seconds). Overall, R-wave increases were highly sensitive (83%), specific (94%), and predictive (94%) for the occurrence of malignant ventricular arrhythmias during experimental acute myocardial ischemia.     

Uremic pulmonary edema

Pulmonary edema fluid analyses and hemodynamic evaluations were performed in two uremic patients with acute pulmonary edema. The colloid osmotic pressure of the pulmonary edema fluid ranged from 57 per cent to 93 per cent that of the serum. Although cardiac function was normal in both patients, the serum colloid osmotic pressure--pulmonary artery wedge pressure gradients were markedly reduced. Uremic pulmonary edema is the result of alterations of pulmonary intravascular Starling forces and increases in pulmonary capillary membrane permeability, allowing for the efflux of protein-rich fluid from the capillaries into the lung.     

Diagnosis of von Willebrand's disease. A comparative study of diagnostic tests on nine families with von Willebrand's disease and its differential diagnosis from hemophilia and thrombocytopathy.

Nine probands with von Willebrand's disease, and their family members, totalling 43 people, were examined. Twenty-seven had a history of bleeding; 29 had an increased factor VIII activity:factor VIII related antigen ratio; 24 had a decreased factor VIII related antigen; 23 had a prolonged bleeding time; 19 had a reduced platelet adhesiveness; 16 had a decreased factor VIII activity; and 14 had an abnormal ristocetin-induced platelet aggregation. Eight members with both normal beleeding time and normal factor VIII activity were found to have other abnormal tests: elevated ratio of factor VIII activity to factor VIII related antigen in seven; decreased factor VIII related antigen in four; and reduced platelet adhesiveness in one. Therefore, ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are more sensitive and may be used for the detection of heterozygous carriers of von Willebrand's disease. Although patients with thrombocytopathy may have a prolonged bleeding time, decreased platelet adhesiveness and reduced platelet aggregation by ristocetin, their factor VIII activity, factor VIII related antigen and ratio of factor VIII activity to factor VIII related antigen are normal and their abnormal ristocetin test cannot be corrected by the addition of factor VIII concentrate. Hemophilic subjects and hemophilic carriers, who are deficient in factor VIII activity, usually have a normal bleeding time, normal platelet adhesiveness, and normal ristocetin test. In contrast to patients with von Willebrand's disease, their factor VIII related antigen is normal or slightly increased and their ratio of factor VIII activity to factor VIII related antigen is significantly reduced. We conclude that ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are not only more sensitive but also more specific for the diagnosis of von Willebrand's disease.     

Alteration of pulmonary function in intravenous drug abusers: Prevalence,severity, and characterization of gas exchange abnormalities

We examined the influence of chronic intravenous drug abuse on respiratory function in 512 consecutive drug addicts by obtaining respiratory histories, pulmonary function tests and chest roentgenograms. Two hundred and fourteen (42 per cent) had carbon monoxide-diffusing capacities (D_lco) of < 75 per cent predicted (mean 65.7 per cent), and in 38 per cent reduced D_lco was the sole pulmonary function test abnormality. Obstructive lung disease attributed to asthma or chronic bronchitis was observed in 6 per cent and a restrictive defect due to interstitial lung disease was observed in 7 per cent. Exercise limitation due to dyspnea among those patients with altered pulmonary function was uncommon except in those with obstructive or restrictive lung disease. Roentgenographic evidence of pulmonary hypertension was not observed in any of the patients. Gas exchange measured at rest and during exercise in 11 patients with a low D_lco and in three patients with restrictive lung disease and a low D_lco revealed an increased alveolar-arterial oxygen difference but normal minute ventilation, dead space-to-tidal volume ratio and absence of abnormal right-to-left shunts. We conclude that alterations in pulmonary function in drug addicts due to foreign particle emboli are very common but that significant respiratory symptoms are unusual and that abnormalities in gas exchange during exercise are mild.     

Fatal outcome in a child with pseudomembranous colitis.

The clinical and histologic changes occurring with antibiotic-associated pseudomembranous colitis are usually reversible with discontinuation of the causative medication. The spectrum of disease patterns ranges from a benign form to a very fulminant and occasionally fatal one. This report describes a child with a severe form of the disease. Despite recognition and sigmoidoscopic confirmation of this syndrome and cessation of antibiotics, his course continued to deteriorate. Sepsis, leukocytosis, refractory diarrhea, and abdominal distension led to exploratory laparotomy. A proctocolectomy was performed for necrosis of the entire colon; however, the patient died of sepsis.