Rate of change of ventricular power: an indicator of ventricular performance during ejection.

An expression representative of the rate of change of ventricular power during ejection was derived. The primary advantages of the expression are its theoretical value and its ability to characterize ventricular performance. The rate of change of ventricular power, measured during ejection, is virtually free of assumptions. It has a fluid dynamic as well as a physiological meaning. It serves in an integrative fashion by combining terms previously shown to be of functional significance. Studies in dogs show that it reflects alterations of the inotropic state yet is relatively independent of alterations of preload or afterload. In nine dogs isoproterenol caused the peak rate of change of power to increase from (10 +/- 2) X 10(8) to (15 +/- 3) X 10(8) dynes-cm. sec.-2 (mean +/- S.E.) (P less than 0.01). Propranolol produced a reduction from (10 +/- 2) X 108 to (6 +/- 1) X 10(8) dynes-cm. sec.-2 (P less than 0.001). An increased afterload induced by angiotensin caused no change of the peak rate of change of power. Augmentation of the preload with dextran, which caused a 40 per cent increase of the end-diastolic volume, produced a statistically insignificant increase of the peak rate of change of power from (12 +/- 3) X 10(8) TO (16 +/- 4) X 10(8) dynes-cm. sec.-2 The rate of change of ventricular power, measured during ejection, therefore appears to be a useful and meaningful indicator of ventricular performance that has many desirable characteristics.     

Ventricular performance measured during ejection: Studies in patients of the rate of change of ventricular power.

An expression indicative of the rate of change of ventricular power was derived and applied to the evaluation of left ventricular performance of patients with angina. Patients were categorized as having normal or abnormal ventricular performance on the basis of the ejection fraction, mean velocity of circumferential fiber shortening, and left ventricular end-diastolic volume index. In those with normal performance, the ejection rate of change of power was (25 +/- 2) times 108 dyne cm. sec. (-2); in patients with abnormal performance it was (11 +/- 1) times 10(8) dyne cm. sec. (-2) (P less than 0.001). There was no overlap of values between categories of patients. Such a clear distinction between categories was not seen with any of the commonly utilized isovolumic indices of performance. The rate of change of ventricular power measured during ejection is free of assumptions, yet has a fluid dynamic as well as a physiological meaning. It serves in an intergrative fashion by incorporating terms previously shown to be of functional significance. Previous studies in dogs showed that it reflected alterations of the inotropic state, yet it was relatively independent of alterations of preload or afterload. It appears, therefore, that it is an indicator of ventricular performance that has desirable characteristics.     

Isovolumic fractional rate of change of power: Its applicability to assessment of ventricular performance in patients

The ratio of the instantaneous isovolumic rate of change of power, normalized to instantaneous isovolumic power, appears to be an expression of physiologic and practical significance. This ratio, termed the isovolumic fractional rate of change of power, describes the capability of the ventricle to sustain, during isovolumic contraction, an acceleration of energy production relative to instantaneous rates of energy production. The expression is independent of assumptions of ventricular geometry, fiber orientation, symmetry of contraction or elasticity of muscle fibers. It was derived upon the basis of established principles of fluid dynamics. The expression serves in an integrative fashion by demonstrating a simple relation between characteristics of performance derived on the basis of fluid dynamics and those derived on the basis of muscle mechanics. In this study, the isovolumic fractional rate of change of power permitted distinction between patients with normal and abnormal ventricular performance (as characterized by the ejection fraction, mean velocity of circumferential fiber shortening and enddiastolic volume index) (P < 0.01). The firm theoretical basis of the isovolumic fractional rate of change of power, and its demonstrated capability to permit identification of patients with normal or abnormal left ventricular performance, recommends it as a meaningful and useful hemodynamic expression.     

Ventricular performance in patients based upon rate of change of power during isovolumic contraction

Energy is expended by the ventricle during isovolumic contraction as the blood within the ventricle is compressed. This isovolumic energy of compression, as well as the isovolumic rate of energy transfer (power) and acceleration of energy transfer (rate of change of power), was calculated in 17 patients with angina pectoris who underwent diagnostic cardiac catheterization. The peak isovolumic rate of change of power in patients with normal left ventricular performance (based upon the ejection fraction, mean velocity of circumferential fiber shortening and end-diastolic volume index) was 31,000 ± 3,000 dynes cm sec^?2 (mean ± standard error), whereas in those with poor ventricular performance it was 18,000 ± 2,000 dynes cm sec^?2 (P < 0.01). None of the patients with poor ventricular performance had a peak isovolumic rate of change of power that exceeded 25,000 dynes cm sec^?2. Overlap between patients with normal performance and those with reduced performance was less with the peak rate of change of power than with peak power, peak rate of change of intraventricular pressure ($\text{dp}\text{dt}$), maximal (dp/dt)/p or Vmax. The derivation of these isovolumic energy transfer rates requires no assumptions related to ventricular geometry or characteristics of muscle fibers. Peak isovolumic rate of change of power may be a useful and sensitive indicator of ventricular performance in patients with coronary artery disease.     

Force-velocity-length relations in man expressed by a single hemodynamic expression: the ejection rate of change of power at peak tension.

An attempt was made to develop a hemodynamic indicator of pump function that relates to the contractile characteristics of cardiac muscle. The ejection rate of change of power has ideal characteristics for this purpose. It is firmly based upon theories of fluid dynamics and its derivation is free of assumptions related to heart structure and function. It is measured as p dQ/dt + Q dp/dt, where p = pressure and Q = flow. When measured at peak tension, the ejection rate of change of power was (12.3 +/- 0.8) X 10(8) dynes cm sec-2 in 11 patients with abnormal ventricular performance (P less than 0.001). Studies in dogs showed no effect of preload or afterload. This suggests a relation to characteristics of muscle fibers, which was shown. If one assumes a thin wall sphere, the ejection rate of change of power at peak tension reduces to the following function of tension (T), fiber length (2 pi r), and rate of shortening (2 pi dr/dt): d(power)/dt = 8 pi T](dr/dt)2 + r d2r/dt2[. Thus, the contractile characteristics of muscle fibers (force, velocity and tension) are related in an uncomplicated fashion by a single and highly discriminating hemodynamic indicator of ventricular performance, the ejection rate of change of ventricular power measured at peak tension.     

The electrocardiogram in acute pulmonary embolism

Electrocardiograms of 90 patients with arteriographically documented acute submassive or massive pulmonary embolism and no associated cardiac or pulmonary disease were studied. Patients were derived from the Urokinase-Pulmonary Embolism Trial National Cooperative Study. In massive embolism, the electrocardiogram was normal in 6% (3 of 50) of patients. With submassive embolism, 23% of patients (9 of 40) had a normal electrocardiogram. Since one or more of the traditional manifestations of acute cor pulmonale (S₁Q₃T₃, right bundle branch block, P pulmonale, or right axis deviation) occurred in only 26% of patients, one could not rely exclusively upon these electrocardiographic abnormalities for the diagnosis of pulmonary embolism. The most common electrocardiographic abnormalities were nonspecific T wave changes which occurred in 42% of patients and nonspecific abnormalities (elevation or depression) of the RST segment which occurred in 41% of patients. Left axis deviation occurring in 7% of the patients was as frequent as right axis deviation. Low voltage QRS complexes, previously undescribed in pulmonary embolism, occurred in 6% of patients. None of the patients had atrial flutter or atrial fibrillation, which appears to occur more typically in patients with pulmonary embolism who have preexistent cardiac disease. All of the varieties of electrocardiographic abnormalities disappeared in some of the patients by 2 wk. Inversion of the T wave was the most persistent abnormality. Larger defects on the lung scan or pulmonary arteriogram occurred in patients with various abnormalities on the electrocardiogram than in patients with normal electrocardiograms. The pulmonary arterial mean pressure and/or right ventricular end-diastolic pressure was significantly higher in patients with several varieties of abnormal electrocardiograms, although the partial pressure of oxygen in arterial blood, in general, did not differ from that in patients with normal electrocardiograms. These hemodynamic correlations, made for the first time in patients, suggest that acute ventricular dilatation, possibly in combination with hypoxemia, is a causative factor of the electrocardiographic changes in acute massive or submassive pulmonary embolism.     

The significance of dissociation of conduction in the canine His bundle. Electrophysiological studies in vivo and in vitro

Fractionated His bundle potentials were induced by ischemia or trauma in 30 anesthetized dogs, in vivo. Functional dissociation, i.e., alteration of the activation sequence of portions of these His bundle potentials was demonstrated in vivo as well as in 10 in vitro preparations of the His-Purkinje system. In vivo, plunge wire and electrode catheters were utilized to record from portions of the His bundle. During vagal-induced slowing of the heart rate, atrial pacing or His bundle pacing, His-Purkinje conduction as measured by the H-V interval was constant over a wide range of heart rates, 50–300/min. One or two hours after anterior septal artery ligation, His bundle damage manifested as split His bundle potentials (H, H′). Atrial pacing or proximal His bundle pacing induced H-H′ delays with concomitant right or left bundle branch block patterns in ECG leads. However distal His bundle pacing at comparable or even higher rates produced normal QRS complexes. In other cases, during atrial pacing or with progressive ischemia at a constant rate, H′ progressively delayed during the H-V interval or even disappeared into the QRS complex with a concomitant occurrence of right or left bundle branch block. In vitro, a dissected septal preparation was studied containing the His bundle, proximal and distal right bundle and left bundle branches. Normal conduction throughout the His-Purkinje system was observed at pacing rates of 30–220/min. Punctate lesions, anatomically placed above the branching His bundle caused tachycardia-dependent, complete bundle branch block with concurrent temporal reversal of proximal and distal His bundle action potentials.These data suggest that ischemic or traumatic lesions in the His bundle may manifest on the electrocardiogram as bundle branch block patterns. From a clinical point of view, a critical site of lesion would markedly increase the liability for A-V block although the electrocardiogram alone would not indicate the actual site of lesion. Predestination of fiber tracts and alternative proposals to the predestination theory are considered to explain QRS aberration due to exclusive His bundle lesions.     

Regional myocardial blood flow and ventricular arrhythmias following one-stage and two-stage coronary artery occlusion in anesthetized dogs

Experiments were performed in 29 anesthetized dogs to compare effects of one-stage and two-stage coronary artery occlusion on ventricular arrhythmias and regional myocardial blood flow (MBF). Two periods of arrhythmias were observed and both were associated with evidence suggesting reentry; i.e., activity in ischemic zone electrograms which bridged the diastolic intervals preceding ventricular ectopic beats. Early ventricular arrhythmias followed progressive deterioration of conduction in the ischemic zone, whereas later arrhythmias occurred unexpectedly with the sudden appearance of bridging activity. One-stage occlusion produced a higher incidence of ventricular arrhythmias and ventricular fibrillation than two-stage occlusion. However, there was no difference in central ischemic zone blood flow, indicating that the protective effect of two-stage occlusion was not due to greater blood flow in this region. These results suggest that factors other than the degree of MBF reduction are important determinants of the incidence and severity of ventricular arrhythmias following coronary artery occlusion.     

Physiologic responses to epinephrine infusion: The basis for a new stress test for coronary artery disease

Since many patients with chest pain cannot exercise adequately, an alternative stress would be useful to evaluate coronary reserve. We studied the physiologic responses to epinephrine to assess its potential. We report on 39 patients with chest pain. Doses from 0.03 to 0.30 μg/kg/min were administered intravenously. Heart rate increased from 72 ± 10 to 86 ± 12 bpm (mean ± SD), systolic blood pressure (BP) from 122 ± 20 to 158 ± 18 mm Hg (increased afterload), and rate-pressure product/100 from 88 ± 21 to 133 ± 18. Rate-corrected pre-ejection period decreased from 141 ± 23 to 92 ± 14 msec and $\text{LVET}\text{PEP}$ ratio from 0.41 ± 0.1 to 0.24 ± 0.05 (increased contractility). Increased afterload and contractility increased myocardial oxygen demand. Simultaneously diastolic time and BP decreased, reducing myocardial blood supply. The endocardial viability ratio fell from 1.27 ± 0.3 to 0.80 ± 0.2. These data suggest that epinephrine infusion would be a useful stress test for coronary disease and are supported by a sensitivity of 87% and specificity of 100% in 23 patients with known coronary anatomy.     

Glomerular thrombosis in spontaneously hypertensive rat. II. Immunofluorescence microscopy. III. Effect of heparin.

This study describes immunofluorescence microscopy (IFM) of kidneys of untreated (or saline-treated) spontaneously hypertensive rats (SHR) and compares the findings with those in age-matched, untreated normotensive Wistar Kyoto rats (WKY), and heparin treated (150 units aqueous heparin subcutaneously twice daily for 30 days) SHR. The rats varied in age from 30 to 112 weeks (before treatment) and were divided into young (< 52 weeks) and old (? 52 weeks) groups. Separate sections from the kidneys of all rats were stained with fluorescein-isothiocyanate-conjugated rabbit antisera against rat γ-G (IgG, IgM, and IgA), IgG, fibrinogen (Fib), third component of complement (C₃), and albumin. The kidneys were evaluated also by light microscopy (LM) in all of the rats and by electron microscopy (EM) in half of the rats. A semiquantitative assessment of IFM findings on a 0 to 4+ scale and scoring of LM findings on a 0 to 39 scale were made. The glomerular lesions were more striking and uniform than the arterial vascular lesions in old SHR. The glomeruli of old SHR (av: 93 weeks) were positive for all the fluorescence materials except albumin. Fib was most marked (3+ to 4+) involving 50 to 75% of the glomeruli in 75% untreated (or saline treated) old SHR. Thrombi were found in the glomeruli also by LM and EM (large amounts of fibrin and platelet aggregates). The arterial vessels were unimpressive by IFM with the exception of those with arteritis in which 3+ to 4+ Fib was found. These findings in untreated (or saline treated) old SHR contrast with the inconspicuous LM, EM, and IFM findings in young SHR and WKY of all ages. Heparin-treated old SHR had significant (P < 0.05) decreases of glomerular fibrinogen (IFM), percentage glomeruli with thrombi (LM), and absence of fibrin and platelet aggregates in the glomeruli studied by EM. In these old SHR, the mean arterial pressure (MAP) was significantly (P < 0.05) lower than the MAP in untreated old SHR. Thus, this study indicates that glomerular thrombosis is a significant renal lesion in old SHR and heparin can alter the glomerular thrombosis and arterial blood pressure. Further study, however, would be necessary to elucidate the mechanisms of the above beneficial effects of heparin.     

Patterns of interectopic activation recorded during pleomorphic ventricular tachycardia after myocardial infarction in the dog

Sustained ventricular tachycardia, consisting of a regular rhythm with 100 or more consecutive ectopic beats, was studied in 14 dogs anesthetized with sodium pentobarbital 4 days after occlusion of the left anterior descending coronary artery. Electrocardiograms were recorded as well as composite (epicardial) and electrode catheter (endocardial) electrograms from the area of infarction. Sustained ventricular tachycardia was induced by atrial or ventricular pacing, or both (180 to 360/min) in 3 of 21 untreated dogs and 11 of 19 dogs treated with methylprednisolone (30 mg/kg body weight, intravenously) given at the time of coronary occlusion. Sustained ventricular tachycardia with two or more QRS configurations occurred in nine dogs, and seven dogs showed both right and left bundle branch block patterns. Ventricular tachycardia was associated with continuous electrical activation in composite epicardial electrograms that bridged interectopic intervals and showed regular patterns of electrical activation that were reproducible with each cardiac cycle. Interectopic activation patterns were distinctive for each QRS pattern. In some instances portions of activation patterns for two different configurations were similar; however, the electrographic configuration immediately before the onset of the QRS complex always differed. During ventricular tachycardia, spontaneous alterations in QRS configuration were observed in two dogs and were induced by atrial or ventricular pacing in five dogs. In all cases changes in QRS configuration during sustained ventricular tachycardia were preceded by changes in diastolic activation patterns.The results suggest that sustained ventricular tachycardia is frequently associated with stable reentrant pathways through areas of critically slow conduction. In this experimental preparation, specific, orderly and reproducible patterns were seen more often than chaotic “localized fibrillation.” Different QRS configurations after changes in interectopic patterns of continuous electrical activation are consonant with changes in specific reentrant pathways through the region of slow conduction.     

Familial absorptive hypercalciuria and renal tubular acidosis.

Hypercalciuria was considered as a secondary condition when associated with familial renal tubular acidosis. Later studies suggested that hypercalciuria could lead to renal tubular acidosis and nephrocalcinosis. Selected members of a family spanning five generations were studied. Renal tubular acidosis was present in eight subjects in three consecutive generations. Increased 24-hour urinary calcium excretion was present in nine subjects in three consecutive generations, alone in the younger generation, and in combination with renal tubular acidosis and nephrocalcinosis in the older generation. Calcium loading tests showed the absorptive nature of hypercalciuria in nine of 18 subjects studied. This report suggests that in this family the absorptive hypercalciuria is an autosomal dominant genetic defect with complete penetrance and variable expressivity which leads to renal tubular acidosis and nephrocalcinosis.     

An analysis of the relationship of malignant lesions of the kidney to hypertension.

This study, designed in a “blind” fashion, presents, for the first time, a relationship of the histopathology of the kidneys with mean arterial blood pressure (MAP) and age in hypertensive species. Kidneys from 46 spontaneously hypertensive rats (SHR) aged 8–104 weeks were studied using light and electron microscopy (LM and EM, respectively), and their findings were compared with those in age-matched 35 normotensive Wistar rats (NR) and 28 Wistar-Kyoto rats (WKY). A scoring system for the severity of the renal changes (index scores) was developed, and the grading of the renal changes was made without any knowledge of age, MAP, or strain of rat from which kidneys were obtained. The severe (or malignant) renal lesions were found only in old SHR (av: 91 weeks), in contrast to mild or moderate renal lesions (benign) in young SHR (52 weeks or less). The findings of highly significant (P <0.01) correlation between age and index scores along with significant (P <0.05) correlation between MAP and index scores in old SHR indicate that both severity of hypertension and age (i.e., duration of hypertension) in hypertensive species and not severity of hypertension alone are determining factors in the pathogenesis of severe (or malignant) renal lesions. Since old SHR are derivative of the same homogeneous population as young SHR, it appears that the malignant renal lesions observed in old SHR are secondary to prolonged severe hypertension. In contrast, the lack of relationship between index scores of benign lesions (Grades II or III) and MAP or age in young SHR indicates independence of benign renal lesions to hypertension.     

Pathophysiologic significance of “stress” or relative polycythemia in essential hypertension

Fourteen patients with essential hypertension (blood pressure 167 ± 2/106 ± 2 [mean ± standard error of the mean] mm Hg) were studied prospectively to determine the pathophysiologic correlates of their “stress” or relative polycythemia. All patients had a high hematocrit level (53.1 ± 0.4 vol percent), contracted plasma volume (16.2 ± 0.4 ml/cm height) and normal red cell mass and serum erythropoietin levels. Blood and plasma viscosity (0.076 ± 0.005 and 0.017 ± 0.001 poise, respectively) were increased, and plasma renin activity in the supine, resting state averaged 1.8 ± 0.3 ng/ml per hour. All patients were treated with methyldopa to achieve normal arterial pressure and the previous determinations were repeated after 1 and 4 weeks of treatment. Reduction of pressure was associated with expansion of plasma volume (P < 0.001) and significant decreases in hematocrit, blood and plasma viscosity and resting plasma renin activity (P < 0.001). Red cell mass and serum erythropoietin levels remained unchanged. Therefore, the so-called stress polycythemia is a pathophysiologic manifestation of the hypertensive vascular disease in which the abnormal hemodynamic and rheologic alterations can be reversed by antihypertensive therapy. The significance of this reversal may have some bearing upon the high prevalence rates of severe cardiovascular complications associated with so-called stress polycythemia and high renin essential hypertension.     

Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-β-disease) a cause or an effect of increased apolipoprotein E levels?

Apolipoprotein E (ApoE; "arginine-rich" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE.     

Sleep disturbances after open heart surgery.

This study was designed to document quantitatively the sleep disturbances that occur after open heart surgery and to investigate a group of patients who underwent a thoracic surgical procedure not involving cardiopulmonary bypass. Nine patients were studied, six after open heart surgery and three after partial or complete pneumonectomy. In each patient, sleep patterns were recorded with use of all night polygraphy before and after operation and for up to 5 weeks on follow-up studies. After open heart surgery, patients manifested considerable suppression of both rapid eye movement and slow wave sleep patterns. In the three patients subjected to thoracotomy these sleep indexes returned to preoperative levels much earlier. Evidence of stage 2 sleep was present in one of the three patients with thoracotomy on the first postoperative night, and in two of the three both rapid eye movement and slow wave sleep returned to preoperative levels by the time of hospital discharge. It is concluded that patients undergoining open heart surgery experience both acute and chronic disruptions of sleep that last well beyond the hospital period of convalescence. These sleep disturbances have considerable relevance for postoperative management.