David G. Greene

The hemodynamic response of man to nor-epinephrine and epinephrine and its relation to the problem of hypertension

Nor-epinephrine (nor-adrenaline, arterenol, amino-ethanolcatechol) is a primary amine identical with epinephrine except for the absence of a methyl group on the nitrogen atom. (Fig. 1.) It was first synthesized by Sto1z3? in 1904. Recently it has been suggested as a possible precursor of epinephrine in vivo5 since it has been shown that methylation occurs readily in the body.” The levo-isomer, possessing approximately twice the activity of the optically inactive preparation, became available in 1948 following resolution of the racemic mixture by Tainter and his group.38 The consistency with which the actions of nor-epinephrine reproduce those of stimulation of sympathetic excitor nerves has led competent investigators to the conclusion that it may be sympathin E, as first suggested by Bacq. 2 In support of this hypothesis Stehle and Ellsworth3’j and Greer and his co-workers20 demonstrated the striking similarity between the effects of nor-epinephrine and those produced by stimulation of the hepatic sympathetic nerves. These observations have been confirmed by von Euler1*~i3 and Gaddum and Goodwin.i8 The strongest evidence in favor of this assumption was von Euler’s demonstration in 1946 of a substance in mammalian adrenergic nerves indistinguishable from nor-epinephrine by biologic and crude chemical tests.‘**13 The thoracic and lumbar sympathetic chain and the splenic periarterial nerves of cattle were particularly suitable sources and contained the equivalent of 10 to 25 pg. of d,l-nor-epinephrine per Gm. of tissue. This substance differed from epinephrine in its blood pressure action following ergotamine. Ergotamine reverses the pressor effect of epinephrine but not of nor-epinephrine. This substance differed likewise from epinephrine in its action on the non-pregnant cat uterus in that relaxation was inconspicuous. It has been assumed that each of the transmitters, epinephrine and nor-epinephrine, carries excitor or inhibitor functions exclusively. But this does not appear to be so because excitor functions are carried not only by nor-epinephrine but also by epinephrine. Epinephrine has been proved to be the transmitter of sympathetic excitation in

Pure congenital pulmonary stenosis and idiopathic congenital dilatation of the pulmonary artery

Abstract 1.1. Sixty-eight cases of pure congenital pulmonary stenosis without abnormal shunts, the diagnosis established at autopsy, have been collected from the literature and the chief clinical and anatomic features are described. 2.2. Eight cases of pure congenital dilatation of the pulmonary artery have been selected from the literature of the last thirty years as being unequivocal examples of that lesion and a summary of the clinical and anatomic features is given. 3.3. Four additional examples of each of these lesions are reported. 4.4. Hemodynamic studies of these eight patients demonstrate the absence of abnormal shunts and the presence of a differential between the systolic pressure in the pulmonary artery and that in the right ventricle. 5.5. A division of these patients into two groups on the basis of the pressure in the right ventricle and the intensity of the pulmonic second sound is proposed. ∗

Effects of heterogeneous myocardial perfusion on coronary venous H2 desaturation curves and calculations of coronary flow

The present investigation was intended to evaluate myocardial inert gas desaturation curves for manifestations of heterogeneous coronary perfusion. The test gas was hydrogen (H(2)) and blood H(2) analyses were performed with a gas chromatograph capable of detecting small but prolonged venous-arterial H(2) differences produced by areas of reduced flow. Curves were initially obtained after 4-min left ventricular infusions of H(2)-saturated saline in six patients with arteriographically proven coronary artery disease, three patients with normal coronary arteries, and nine closed-chest dogs. The dogs were studied before and after embolic occlusion of a portion of the left coronary artery. Although the slopes of their semilogarithmically plotted venous desaturation curves varied with time before embolization, they showed more distinct deviations from single exponentials after embolization (after H(2) concentrations had fallen below 15% of their initial values). The human curves divided similarly, those from coronary artery patients deviating appreciably from single exponentials. A similar separation was also evident in studies of coronary venous-arterial H(2) differences after 20 min of breathing 2% H(2): data were obtained in four dogs before and after coronary embolization, and in three normal patients, and five patients with coronary artery disease. Additional data indicated that the findings were not the result of right atrial admixture in sampled coronary venous blood, although admixture occurred frequently when blood was sampled in the first 2 cm of the coronary sinus (as seen in the frontal projection). Finally, average coronary flows calculated from a given set of data varied significantly with different methods of calculation. Areas of below-average flow seemed likely to be overlooked when single rate constants of desaturation, relatively insensitive analytical techniques, or relatively short periods of saturation and (or) desaturation are employed.

The valve-closing function of the right atrium:A study of pressures and atrial sounds in patients with heart block

I N second degree or complete heart block, prolonged ventricular diastoles allow the atria1 contraction cycle to be studied in a pure form. Auscuitation may reveal two sounds in association with these isolated atria1 contractions (Fig. l), here referred to as the first and second atria1 sounds; Lewis [7] suggested that the second atria1 sound was due to closure of the atrioventricular valves. To test whether the tricuspid valve can be closed by atria1 contraction, four subjects with heart block have been studied by right heart catheterization. Theory suggests that if the tricuspid valve does close following atria1 contraction it will trap blood in the ventricle, ventricular pressure will remain elevated and a reversed pressure gradient will develop across the valve with the lower pressure in the atrium. The catheter pressure measurements were designed to detect such a reverse gradient, if present.

Evaluation of Venous Bypass Grafts from Aorta to Coronary Artery by Inert Gas Desaturation and Direct Flowmeter Techniques

Blood flow through aorta-to-coronary artery bypass grafts has been measured selectively in 16 patients at or within 6 wk after operation. Inert gas desaturation curves were obtained from coronary venous blood samples after a 7-15 min infusion of dissolved H(2) directly into the graft. Samples were analyzed chromatographically and curves resolved to 1-3% of initial H(2) concentrations. Average flow per unit volume (F/V) was 67+/-21 (sd) ml/min per 100 g. Semilogarithmic plots showed F/V to be distributed heterogeneously in every case. In nine studies at operation, H(2) measurements of average F/V were combined with electromagnetic measurements of total flow to estimate revascularized tissue mass. Electromagnetic flows ranged from 25 to 170 ml/min and averaged 69 ml/min. Tissue mass ranged from 46 to 155 g and averaged 88 g. We conclude that bypass grafts provide nutritive flow to significant amounts of myocardium at and shortly after operation. However, nutritive flow is not distributed evenly throughout the revascularized segment. The majority of the segment has a F/V within the accepted range of normal but there remain areas in which F/V is reduced significantly. The combination of inert gas and electromagnetic techniques allows a revascularized area to be characterized in terms of total flow, F/V, and tissue mass.

Excision of Akinetic Left Ventricular Wall for Intractable Heart Failure

Excerpt The advent of cineventriculography has made it clear that there is a spectrum of motion disturbances involving the left ventricular wall. Akinesis, or lack of wall motion, is one serious co...

Cardiopulmonary function studies in a patient with ligation of the left pulmonary artery

Abstract A case is reported in which cardiopulmonary function studies were performed on a patient two years after the left pulmonary artery was ligated. Cardiac catheterization revealed normal pressures in the pulmonary artery as well as in the chambers of the right side of the heart. The results of pulmonary function tests were almost completely within normal limits. The only abnormalities found were a slight increase in cardiac index and hyperventilation under all conditions of observation. However, bronchospirometry disclosed a marked Table III Results of Cardiocirculatory Studies NormalObservedPressures in mm. of mercuryPulmonary artery, systolic 2 )3.05 + 0.64.23 limitation of gas exchange in the left lung, with carbon dioxide output limited to a lesser degree than oxygen consumption. These findings are consistent with the assumption that anastomoses from the bronchial artery result in a considerable blood flow through the pulmonary capillary bed of the left lung.

Measurement of cardiac output in man with a nonrecirculating indicator

The present investigation was undertaken to evaluate the utility of constant-rate injection of a nonrecirculating indicator (H(2)) for the measurement of cardiac output in man. 42 patients were studied during cardiac catheterization and 8 during acute complications of arteriosclerotic heart disease, including acute myocardial infarction. Pulmonary (or systemic) arterial H(2) concentration was measured chromatographically from 2.0 ml blood samples drawn during constant-rate injection of dissolved H(2) into the systemic venous circulation (or left heart). The chromatograph was a thermal conductivity unit housed in a constant-temperature water bath to achieve an improved signal-to-noise ratio. Intrapulmonary H(2) elimination from mixed venous blood was measured directly in 14 patients and averaged 98 +/-1.5% (SD). Reproducibility of output measurements was evaluated using triplicate determinations obtained over 45-60 sec in 25 consecutive patients. Coefficients of variation (SD/Mean x 100) averaged 3.4 +/-2.0%, making it possible to evaluate relatively small changes in measured output with conventional statistical tests. Individual measurements could be repeated at 10-15 sec intervals. Comparisons of H(2) and direct Fick measurements were made in 14 patients; H(2) outputs averaged 106 +/-4% (SEM) of Fick outputs (P > 0.1). Comparisons of H(2) and dye dilution measurements were performed in an additional 24 patients. Seven had angiographically-negligible valvular regurgitation and dye outputs averaged 106 +/-3% of H(2) outputs (P > 0.1). 17 had moderate-to-severe regurigation and dye outputs averaged 91 +/-4% of H(2) outputs (P < 0.05), suggesting a small but systematic error due to undetected recirculation of dye. The H(2) technique appears advantageous for rapidly repeated determinations of output, for quantitation of small changes in output, and for situations in which recirculation of conventional indicators is a potentially significant problem.