Juan R. Serur

Influence of Right Ventricular Filling Pressure on Left Ventricular Pressure and Dimension

The effects of alterations in the diastolic filling pressure of the right ventricle on left ventricular (LV) geometry and filling pressure were studied in six isolated, supported canine hearts. This experimental preparation permitted graded increments in right ventricular (RV) end-diastolic pressure while LV cardiac output, heart rate, and mean aortic pressure were held constant. Endocardial radiopaque markers were placed in the ventricular septum, the anterior wall, the posterior wall, and the free wall in a plane perpendicular to the aortoapical axis. LV end-diastolic dimensions were recorded by x-ray cinematography at 60 frames/sec. The effects of varied RV end-diastolic pressure (0–16 mm Hg) on LV end-diastolic pressure and dimensions were studied at several LV cardiac outputs (780–2880 ml/min) and at several initial LV end-diastolic pressures (1–18 mm Hg). Increments of 5 mm Hg in RV end-diastolic pressure increased LV end-diastolic pressure 2.3 mm Hg. The septum-to-free wall distance decreased by 4.5% from the control distance, but the anterior-to-posterior dimension increased by 4.4%.Thus, LV end-diastolic pressure and LV end-diastolic dimensions were significantly related to RV end-diastolic pressure; LV end-diastolic geometry was increasingly distorted at elevated RV end-diastolic pressure. These data suggest that the high RV filling pressures that characterize certain diseases can secondarily alter LV filling pressures and geometry.

In vivo coronary angioscopy.

The feasibility of in vivo coronary angioscopy was tested utilizing a 1.8 mm angioscope in vessels where blood had been replaced by optically clear liquids, including a new perfluorocarbon emulsion. After trials in postmortem canine and human coronary arteries, in vivo intraluminal visualization was accomplished in the dog with a catheterization technique and in patients during open heart surgery. The results demonstrate the feasibility and potential clinical usefulness of direct visualization of intravascular anatomy and disease, analogous to endoscopy of other organ systems.

Uptake of hematoporphyrin derivative by atheromatous plaques: Studies in human in vitro and rabbit in vivo

Hematoporphyrin derivative, a photosensitive material used to identify and treat neoplastic tissue in humans, has been found to localize in atheromatous plaques in animals and has recently been found in postmortem human atherosclerotic plaques. It is not known whether human plaques take up hematoporphyrin derivative in vivo. In five patients undergoing surgical vascular procedures, specimens containing atheromatous plaques were removed and immediately incubated in autologous oxygenated blood at 37 degrees C with hematoporphyrin derivative at a clinically relevant concentration for 2 hours. On exposure to ultraviolet light, porphyrin fluorescence was noted throughout each plaque, whereas adjacent plaque-free tissue showed no fluorescence. To compare in vitro with in vivo hematoporphyrin derivative uptake by plaques, the fluorescence of three types of arterial lesions (induced by a high cholesterol diet, catheters or balloon injury) was studied in 16 New Zealand White rabbits. Each lesion fluoresced selectively with the same intensity whether hematoporphyrin derivative exposure was performed in vitro or in vivo. Fluorescence microscopy did not show a difference in the pattern of hematoporphyrin derivative fluorescence between in vitro and in vivo specimens. The results suggest that human atheromatous plaques should take up hematoporphyrin derivative in vivo and are, therefore, potentially suitable for photochemical treatment as a new therapeutic approach to atherosclerosis.

Respiratory acid-base changes and myocardial contractility: Interaction between calcium and hydrogen ions ☆

Abstract The mechanism whereby respiratory acid-base changes alter myocardial contractility is poorly understood. Accordingly, 46 cat right ventricular papillary muscles contracting isometrically at 30°C were studied while varying both the pH and [Ca 2+ ] of the bathing medium. The pH changes were induced by varying the PCO 2 of the gassing mixture. A decrease in pH from 7.45 to 7.10 in the presence of 2.5 m m Ca 2+ caused a rapid fall in active force and rate of force development ( d F d t ) to levels 76% of control followed by a gradual recovery to approximately 89% of control during a 60 min observation period despite continued acidosis. Increasing the [Ca 2+ ] to 5.0 m m markedly attenuated the negative inotropic effects of hypercarbic acidosis. Increasing the pH from either 7.10 to 7.45 or 7.45 to 7.75 caused a rapid 15% increase in active force and d F d t followed by a return to near control levels after 60 min. The biphasic contractile response to either respiratory acidosis or alkalosis was not influenced by pretreating the muscles with 1 × 10 −6 m propranolol. In 10 additional muscles series elastic load-extension relations at varying pH levels were determined using standard quick-release techniques. Respiratory acid-base changes did not alter the measured series elastic properties. These findings indicate that the contractile effects produced by carbon dioxide-induced pH alterations are exerted at the level of the contractile element and that the muscle has the intrinsic capacity to attenuate these inotropic effects with time. Furthermore, our results suggest that the contractile effects produced by changing [H + ] may involve an interaction with Ca 2+ at a sarcolemmal or intracellular binding site.

Experimental myocardial ischemia. III. Protective effect of glucose on myocardial function

Abstract Glucose has been long known as an important substrate for muscle cells and a number of laboratories have demonstrated that carbohydrate metabolism can contribute significantly to energy production both in aerobic and anerobic heart muscle. It has been suggested that these findings may have additional application in localized myocardial ischemic and infarction. Accordingly, experiments were performed to determine the effect of glucose on the mechanical and electrical activity of the heart. Left ventricular pressure (LVP), left ventricular d p d t ( LVd p d t , left ventricular end diastolic pressure (LVEDP), and the incidence of ventricular premature beats (VPB) and ventricular fibrillation (VF) were determined before and after ligation of the anterior descending coronary artery in three different canine heart experimental models. Thirty minutes after ligation of the left anterior descending coronary artery, the mean left ventricular pressure and mean left ventricular d p d t in the control group had decreased by 85 ± 6% and 74 ± 5% respectively. Under similar conditions glucose treatment produces an increase in left ventricular pressure and left ventricular d p d t of 111 ± 5% and 123 ± 8% respectively. The simultaneously measured mean left ventricular end diastolic pressure was 7.2 ± 0.9 ml for the control group and 3.7 ± 1 for the glucose treated group. Eighty-three percent of the control dogs developed ventricular ectopic activity. Fifty-eight percent of the control hearts developed ventricular fibrillation. In contrast, only 10% of the glucose treated hearts demonstrated ventricular ectopic activity and only 10% developed ventricular fibrillation. Glucose, as a bolus, consistently improved myocardial contractility and prevented ventricular fibrillation even after serum osmolality and serum glucose levels had returned to normal. These results demonstrate that glucose has a protective effect on the electrical and mechanical function of the canine heart during acute segmental myocardial ischemia. These findings may have application in the treatment of acute myocardial infarction in man.

An experimental model of acute and subacute viral myocarditis in the pig

Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST-T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions.

Differential effects of sodium meglumine calcium metrizoate on the inotropic state of normal and ischemic myocardium.

Sodium meglumine calcium metrizoate was injected into isolated blood-perfused canine hearts to evaluate the effect of contrast agents containing calcium on normal and ischemic myocardium. Under normal perfusion pressure and mild ischemia, this contrast agent produced a positive inotropic effect, but during profound ischemia, this positive effect was followed by a period of myocardial depression. These findings indicate that the addition of an inotropic agent to contrast medium can produce a paradoxical depressant effect which can be deleterious to the ischemic myocardium.

Experimental myocardial ischemia: dynamic alterations in ventricular contractility and relaxation with dissociation of speed and force in the isovolumic dog heart.

Although the time course of changes in myocardial function during ischemia has been demonstrated for tbe papillary muscle, this time course in tbe intact heart is less well understood. Accordingly, in 24 isolated, isovolumic, perfused dog hearts, coronary perfusion pressure (PP) was lowered to various fixed levels. Left ventricular developed pressure (LVP) rapidly fell and reached 63 ± 3% of control at 1 minute of ischemia and 50 ± 5% at 6 minutes; this was due primarily to an abbreviation of time to peak tension (TPP). dP/dt was 70 ± 3% of control at 1 minute and 56 ± 5% at 6 minutes. The rate of relaxation as reflected by negative dP/dt declined as well to 49 ± 4% of control at 1 minute of ischemia and to 41 ± 4% of control at 6 minutes. These changes were directly correlated with the decrease in PP. When PP was restored to normal, an overshoot of LVP and dP/dt was noted, peaking at 1 minute, returning to control by 5 minutes, and then gradually declining to 90 ± 2% of control following 25 minutes of recovery. Depression of the rate of relaxation was reduced, but persisted throughout recovery. Diminution of force development early in ishcemia is due primarily to decreased duration of contraction accompanied by a decrease in relaxation rate. Later, the rate of force development also falls, but some preservation of force development may result from the return toward normal of tbe duration of contraction.

Intravascular Application Of Hematoporphyrin Derivative Photodynamic Therapy

Photodynamic therapy (PDT) of diseased tissues with hematoporphyrin derivative (HPD) within the cardiovascular system could be performed with a light-emitting antra-arterial optical fiber. However, the penetration of light at 631 nm through oxygenated whole blood first needs to be studied. In vitro studies were, therefore, performed to measure the transmission of 631 nm light, generated by an argon-ion pumped dye laser, through whole blood and serial dilutions of whole blood with the relatively translucent blood substitute Fluosol-DA. The results indicate that whole blood attenuates 631 nm light far greater than tissues, where HPD-PDT is currently applied, and that a 2 mm thickness of whole blood at a normal hematocrit may prevent a photodynamic tissue reaction when a conventional light dose is applied. Preliminary observations in rabbits treated in vivo with hematoporphyrin and 631 nm light via an intra-aortic optical fiber, with and without Fluosol-DA hemodilution, confirm these results. Hemodilution of whole blood with translucent liquids will enhance photodynamic tissue reactions and may be a necessary adjunct when this therapy is applied within the cardiovascular system.

Experimental chronic left ventricular akinesis. Hemodynamic effects of atrial pacing.

Experimental myocardial infarction resulting in chronic left ventricular akinesis was created in eight mongrel dogs using a two-stage ligation and agar injection of branches of the left coronary artery. Eight weeks after infarction, all had akinetic regions involving 20 to 35% of the left ventricular wall and were in congestive heart failure at rest as evidenced by resting tachycardia, 120 ± 13 beats/min; reduced ejection fraction, 0.46 ± 0.03; and elevated left ventricular end-diastolic pressure (LVEDP), 40 ± 3 mm Hg. Atrial pacing resulted in substantial reduction in LVEDP (40 ± 3 to 14 ± 3 mm Hg; P < 0.001) while cardiac output remained unchanged (3.2 ± 0.4 liters/min). Pacing caused significant reductions in end-diastolic volume (63 ± 8 to 52 ± 7 ml; P < 0.001) and ejection fraction (0.44 ± 0.02 to 0.32 ± 0.01; P < 0.001), but end-systolic volume was unchanged (36 ± 6 ml) suggesting that improvements in left ventricular performance were not related to increased contractility. This study characterizes the hemodynamic alterations in experimental left ventricular akinesis and suggests that atrial pacing at high rates may improve cardiac performance without a demonstrable increase in intrinsic myocardial contractility.