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Biomedical subjects

G C Taichman

Publications and source records attributed to G C Taichman.

At least 19 recordsLinked to original sources

Changes in regional blood flow distribution induced by infusions of dopexamine hydrochloride or dobutamine in anesthetized dogs.

Systemic blood flow distribution was determined using radionuclide-labeled microspheres in anesthetized dogs during infusions of dopexamine hydrochloride or dobutamine. Three doses of the drugs were administered intravenously, in the form of 22-minute infusions (3 X 10(-9), 10(-8), 3 X 10(-8) mol/kg/min [1.3 to 12.9 micrograms/kg/min] dopexamine hydrochloride and 10(-8), 3 X 10(-8), 10(-7) mol/kg/min [3.4 to 34.0 micrograms/kg/min] dobutamine). Both drugs induced dose-dependent acceleration of the heart rate. Blood pressure was maintained during infusions of dobutamine, while dopexamine hydrochloride induced arterial hypotension. As a result, the increments in heart rate-blood pressure product were smaller with dopexamine hydrochloride than with dobutamine. Dopexamine hydrochloride induced blood flow increments in the heart, several sections of the gastrointestinal tract, kidney and skeletal muscle. Quantitatively, these changes were different from those induced by dobutamine in only 3 organs. The myocardial blood flow increments during infusions of dopexamine hydrochloride were smaller than those of dobutamine, whereas in the stomach and in skeletal muscle, the flow increments induced by dopexamine hydrochloride were significantly greater than those induced by dobutamine. The findings suggest that dopexamine hydrochloride, by virtue of its agonist activity at beta 2-adrenergic and DA1- and DA2-dopaminergic receptors, is a powerful vasodilator.

Abdomen↗

Cardiac transplantation: the ideal myocardial temperature for graft transport.

The ideal preservation method and cooling temperature for transport of donor hearts are not known. Serious derangements in myocardial relaxation are well described with different methods of cooling. To assess this problem, human right atrial trabeculae contracting isometrically at 34 degrees C in vitro were subjected to hypothermic arrest at 1, 4, 12, and 20 degrees C for 1, 2, 4, 24, and 48 hours. Control conditions were resumed, and myocardial mechanical recovery was assessed over 1 hour. Contraction was 50% depressed after a 1- to 2-hour exposure to 1 degree C and was almost completely arrested following a 4-hour exposure. Muscles cooled to 4 degrees C recovered poorly, whereas those cooled to 12 and 20 degrees C did well. In the latter 2 groups, force development increased rapidly on rewarming and exceeded the precooling contraction force (p less than 0.05). A 100% increase in relative resting force was seen in muscles cooled to 1 and 4 degrees C (p less than 0.05). This finding suggests a failure of calcium homeostasis at very low temperatures. We conclude that atrial preservation is optimal at about 12 degrees C.

Adult↗

Coronary vascular actions of stroma-free hemoglobin preparations.

The left anterior descending coronary artery was cannulated in anesthetized, open-chest dogs for use as a coronary test bed to assess the coronary vascular actions of oxygenated, unmodified and pyridoxylated, partially cross-linked (polymerized), stroma-free hemoglobin solutions (SFHS). The actions of these SFHSs were assessed in this test bed, by comparison with perfusion with whole blood. Unmodified SFHS caused significant vasoconstriction, whereas pyridoxylated, partially polymerized SFHS did not do so. The existing coronary flow during perfusion with either SFHS preparation, under basal conditions, did not increase during intracoronary infusion of adenosine. Coronary flow-autoregulation was also altered during perfusion with either SFHS, because the "normal" reactive hyperemia response, observed in the control experiments, was not seen. These findings suggest that both unmodified and pyridoxylated cross-linked (70% polymers) hemoglobin preparations possess some vascular activity when tested in the canine coronary circulation.

Animals↗

The myocardial contractile responses to protamine sulfate and heparin.

The administration of protamine sulfate for the reversal of heparin anticoagulation has been associated with adverse hemodynamic changes including hypotension and decreased cardiac output. The possible direct toxic effect of protamine on human right atrial trabeculae contracting isometrically in vitro was studied. Muscles were stimulated to contract at 1 Hz in Tyrode's solution (maintained at 34 degrees C, pH 7.4) into which protamine was continuously added. Following a polynomial regression analysis, a parabolic dose-response curve resulted. The equation was: y = 95.13 + 38.76x - 278.71x2 where y = relative developed force and x = concentration of protamine (milligrams per milliliters) (r = 0.82). The estimated concentration of protamine resulting in 50% developed force was 0.48 mg/ml. In a second series of experiments, protamine was added to the bath along with a neutralizing amount of heparin. This resulted in a limited reduction in the fall of relative developed force. Thus, protamine in high concentrations alone or in complex with heparin has a direct toxic effect on human myocardial muscle mechanics, and care is warranted in its clinical use.

Depression, Chemical↗

The use of cardio-green for intraoperative visualization of the coronary circulation: evaluation of myocardial toxicity.

Direct visualization of the extent and adequacy of the coronary blood flow distribution can be performed intraoperatively with an intracoronary injection of indocyanine green dye (Cardio-Green). Because Cardio-Green is potentially toxic to the myocardium, we studied its effects on the mechanical performance of cardiac muscle, using human right atrial trabeculae contracting in vitro. In the first series of experiments, muscles were exposed to 25 mg/ml of Cardio-Green (a concentration 100 times greater than what would be used clinically); no significant alteration in cardiac mechanics was found when evaluated by the force-frequency relationship. To establish the concentration at which Cardio-Green would be toxic, an accumulated dose-response relationship was determined. When a polynomial regression analysis was done, the results best fit a parabolic curve: At high doses, Cardio-Green was found to be negatively inotropic. The estimated concentration that would evoke a 50% decrease in developed force was 41.96 mg/ml. The results show that intracoronary injection of Cardio-Green at clinical doses up to 0.3 mg/ml does not affect myocardial muscle performance. Safe intraoperative use depends on appropriate low doses.

Journal Article↗

Direct effects of autotransfused blood on myocardial muscle mechanics in man.

Homologous blood transfusions carry risks--febrile reactions, isoimmunization incompatibility reactions and transmission of infectious diseases such as AIDS and hepatitis. Although autotransfusion techniques will reduce the need for banked homologous blood, autologous shed blood does contain various cellular fragments that may act directly as myocardial depressants. Accordingly, the myocardial muscle mechanical properties of isolated human right atrial trabeculae contracting in vitro were measured in a bath containing either blood collected in the Sorensen ATS Autotransfusion Receptal unit or arterial autologous blood. Muscles were tested randomly in each solution by measuring their isometric resting and developed forces and the mean rate of developed force at different stimulation rates (force-frequency relation). In addition, biochemical, hematologic and immunologic assays were performed on each blood specimen. Significant increases (p less than 0.05) in potassium and plasma-free hemoglobin indicated that cell disruption had occurred in blood collected in the autotransfusion apparatus; however, there was no statistically significant difference in mechanical performance between muscles contracting in either solution. From these results, the authors conclude that autotransfused blood does not directly affect human heart-muscle mechanics.

Adult↗

The relationship between pericardial pressure and right atrial pressure: an intraoperative study.

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.

Aged↗

Regional myocardial blood flow during pericardial tamponade.

The relative changes in myocardial blood flows within different parts of the heart were measured in anaesthetized thoracotomized dogs during and following effusive pericardial tamponade. Blood flows measured in a group of animals bled to the same arterial hypotensive levels served as experimental controls. The results demonstrate that regional myocardial blood flows to all areas were severely reduced during tamponade. Regional differences in the relative responses were evident; right and left atrial flows decreased more than left ventricular or septal flows which in turn decreased more than right ventricular endocardial flows decreased more than epicardial and the flow within the left side of the septal wall decreased more than the right. Although decreases in aortic pressure and ventricular volumes can account for some of these changes in flow seen in tamponade, alterations in extravascular compression appear to further reduce the myocardial perfusion and may be responsible for the differences in regional responses. In further experiments when the pericardial cavity was drained following 2 h of tamponade, a hyperemic response was seen throughout the heart indicating that the myocardial flow during tamponade may have been insufficient to meet the cardiac demands. In conclusion tamponade appears to result in a disproportionate decrease in myocardial blood flow to various parts of the heart which cannot be explained on the basis of a decrease in blood pressure or a reduction in ventricular volume.

Animals↗

Human atrial trabeculae: an experimental preparation for studying myocardial response to perioperative manipulations.

Trabeculae taken from discarded human right atrial specimens during cardiac surgery provide a useful preparation for studies in myocardial physiology and pharmacology. Three extrinsic measurements that have a marked effect on contraction of this preparation are temperature, stimulation frequency and calcium ion (Ca2+) concentration. There is a large decline in developed force below 30 degrees C. The optimal stimulation frequency (temperature 34 degrees C, Ca2+ concentration 2.5 mM) is 1 Hz. The Ca2+ level required to give half maximal force development is 2.0 mM. In a series of 46 atrial trabeculae (approximately 1 mm in diameter) from 33 patients, the authors found a mean contraction tension of 1.37 +/- 0.09 g/mm2 (+/- standard error) (temperature 34 degrees C, stimulation frequency 1 Hz, pH 7.4, Ca2+ concentration 2.5 mM) at maximum force. The preparation appears to have great potential for the study of perioperative manipulation on myocardial function.

Adult↗

Myocardial responses to acute global ischemia and reperfusion.

Effects of 15 to 120 minutes of global myocardial ischemia without coronary occlusion followed by 60 minutes of reperfusion were examined in anesthetized dogs on total coronary bypass. Thirty minutes or less of global ischemia was found to be fully recoverable, while longer periods of ischemia were associated with irreversible damage. Total and regional myocardial flows and myocardial oxygen consumption did not recover in animals subjected to 60 minutes of global ischemia, while hemodynamic dysfunction became apparent only after 90 minutes of global ischemia. These results indicate that global myocardial ischemia, like coronary artery ligation, will produce functional impairment during reperfusion which is dependent on the duration of the insult.

Animals↗

Effects of hydrogen peroxide on isolated myocardium.

In a preliminary series of experiments, the mechanical responses of myocardium to dilute solutions of hydrogen peroxide were examined in 19 isolated rat papillary and 25 human atrial muscles under normoxic and hypoxic conditions. When a single dose (0.5 to 1..0 ml) of 3% hydrogen peroxide [final concentration 0.01% to 0.02%] was added to normoxic muscle, developed force rose significantly [P less than 0.05] followed by a gradual increase in resting force resulting in contracture. A similar result was obtained in normoxic hypodynamic human atrial muscle. Under hypoxic conditions a singly dose of hydrogen peroxide caused a significant [P less than 0.05] improvement in mechanical properties of both preparations: developed force increased while resting force decreased However, these changes were followed by a progressive irreversible contracture. In contrast, when a 0.06% solution of hydrogen peroxide was slowly infused at a constant rate [2 ml/min], human atrial muscle showed a significant [P less than 0.05] increase in developed force and a significant [p less than 0.05] decrease in resting force from the hypoxic state while the rat papillary muscle only showed a significant [P less than 0.05] increase in resting force. Contracture did not occur in either preparation. The authors conclude that controlled contact between cardiac muscle and dilute solutions of hydrogen peroxide can alter the mechanical characteristics of myocardial tissue.

Animals↗

A relationship between ultrasonic intensity and changes in myocardial mechanics.

The effects of ultrasound on the mechanical properties of isometrically contracting rat papillary muscle have been studied as a function of the intensity of the ultrasonic irradiation. Each muscle was subjected to irradiation at 1.1., 2.2, and 3.3 W/cm2 at a frequency of 2.3 MHz. Ultrasonic irradiation caused heating in the vicinity of the muscle; thus it was necessary to separate the pure thermal and ultrasonic effects. After irradiation the bath temperature was increased so that the muscle reached the same temperature which occurred during ultrasonic irradiation. The mechanical parameters measured during the equivalent thermal procedure were compared with the parameters during irradiation. There was a significant (p less than 0.05) decrease in resting force which was significantly different from the equivalent thermal intervention and could be related to the ultrasonic intensity. Thus, the effect of ultrasound on rat papillary consists of two components, a thermal component which affects all parameters studied and a nonthermal component which affects only the diastolic force.

Animals↗

Effectiveness of intra-aortic balloon counterpulsation on systolic unloading.

The therapeutic benefit of intra-aortic balloon pumping (IABP) is believed to result from the combined action of reducing myocardial demand (systolic unloading) while improving myocardial supply (diastolic augmentation). However, the relative importance of these aspects has not been fully understood. Accordingly, the systolic unloading responses to IABP were studied in 13 dogs on total coronary bypass. By perfusing the coronary circulation from an extracorporeal source at a controlled pressure the authors were able to analyse the systolic unloading responses without diastolic augmentation directly altering coronary flow. The results suggest that IABP is effective only in reducing myocardial demand at normotensive levels; IABP during hypotensive states did not assist the failing heart mechanically by systolic unloading. Therefore the therapeutic action of IABP must result from increases in coronary blood flow by diastolic augmentation.

Animals↗

The effects of ultrasound on the mechanical properties of rat cardiac muscle.

The mechanical properties of cardiac muscle during ultrasonic irradiation have been studied in vitro. Left anterior papillary muscle from normal rats was suspended in buffered lactated Ringers solution equilibrated with 95% O2, and 5% CO2 and maintained at 20 degrees C. The muscles were stimulated to contract isometrically three times per minute at the length which produced maximum tension. Each muscle was irradiated with a MHz ultrasound at an average power of 2.4 Wcm-2 for a period of 10 min with a 10 min recovery period. Irradiation caused an average increase in temperature of the muscle of 1.7 +/- 0.2 degrees C (mean +/- SEM). Irradiation caused the resting tension (1.46 +/- 0.13g) to decrease by 17.8 +/- 4.7% and the developed tension (3.33 +/- 0.61g) to decrease by 4.1 +/- 0.9%. Since changes in contractile properties have been reported with temperature the bath temperature was raised and changes in contraction observed. When compensated for effects of temperature, the changes in resting tension became - 13.3 +/- 4.1% while the change in developed tension became + 1.6 +/- 2.3%. The change in resting tension is highly significant (p less than 0.05 paired t-test) while the change in developed tension is not. Thus 1 MHz ultrasound at an intensity of 2.4 Wcm-2 appears to affect resting tension of cardiac muscle without affecting the active tension. Since changes in cardiac mechanics of this type have not been described previously the effects of ultrasound appears to be unique.

Animals↗

Acute cardiac failure: the relation between coronary flow and oxygen consumption.

In an initial study with dog hearts functioning in situ on total coronary bypass, we demonstrated that predetermined levels of reduced cardiac pump function could be achieved by reducing total coronary flow through changes in the perfusing pressure. In subsequent experiments, oxygen values were measured so that changes in myocardial aerobic consumption in response to brief (3 minute) alterations in coronary perfusing pressure could be determined as well. As a result significant linear correlations were found between coronary flow and myocardial oxygen availability (r = 0.98), oxygen extraction (r = 0.49) and oxygen consumption (r = 0.92). These changes in oxygen values paralleled those in cardiac function (stroke work, r = 0.84).

Animals↗

Effect of age on passive elastic stiffness of rat heart muscle.

A thick-wall spherical model for the rat left ventricle was used to deduce passive wall stiffness from diastolic pressure-volume data. This was done for rats in three age classes: young (1 mo), adult (17 mo) and old (17 mo). The model was based on finite deformation elasticity theory consistent with the magnitude of observed deformation. A least-squares procedure was used to determine elastic constants in postulated nonlinear stress-stretch relations for the myocardium. It was found that at a given level of stress, wall stiffness for ventricles in the young age class was consistently greater than wall stiffness in the other two classes. In addition, the difference in wall stiffness between rats in the adult and old age classes was found to be approximately 10%.

Aging↗

Acute cardiac failure: the relation between coronary flow and cardiac function.

To study the effects of acute coronary hypotension on the working dog heart in situ, both coronary arteries were cannulated and perfused with oxygenated blood at controlled pressures (40 to 120 mm Hg). At a perfusion pressure of 120 mm Hg, total coronary artery flow appeared to be sufficient (0.95+/-0.08 ml/min-g) to maintain normal cardiac performance for a 2.5-hour observation period. During incremental decreases in coronary perfusion pressure, significant linear correlations were found between coronary flow and cardiac index (r=0.84), left ventricular maximum dP/dt (r=0.83), stroke index (r=0.82), stroke work (r=0.83) and mean arterial pressure (r=0.62). During simulated shock conditions (systolic arterial pressure, less than 75 mm Hg), relative reductions in coronary flow (-60.9+/-4.0%) paralleled changes seen in cardiac function and persisted for 28+/-4 min.

Animals↗