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Biomedical subjects

S K Brockman

Publications and source records attributed to S K Brockman.

At least 19 recordsLinked to original sources
PubMed1990

Theoretical and experimental analysis of right ventricular bypass and univentricular circulatory support.

In this paper we examine the dynamic coupling between cardiac pump events and vascular arterial-venous factors that regulate the rate of blood flow around the circulation. A series of experiments were designed to test the feasibility of maintaining vascular and pulmonary function in the absence of the right heart and to characterize the physiologic and hemodynamic consequence of such an exclusion. Theoretical analysis of the cardiovascular system (excluding neuro-humoral factors) using both lumped time invariant and distributed compartmental mathematical equivalent representations, demonstrated that a change in cardiac output (Q) has an inverse-linear effect on venous and direct-linear effect on arterial pressure. A single blood-pump, in a form of a mechanical substitute or the biologic left-heart, alone can support the circulation. Cardiac output reserve is limited (50 percent of normal) because of the rapidly diminishing pulmonary venous-pressure as outflow is increased, irrespective of the pump's specific characteristics. Experiments in animals combined with mock-circulatory studies and computer modeling confirm that near normal flow can be sustained by increasing the stressed blood volume or reducing selectively the systemic venous compliance (i.e., inflatable pressure suit, venous constriction, intra-abdominal compression maneuvers, etc.). The right heart is not essential for normal pulmonary circulation but serves to maintain low systemic venous pressure and relatively high left-heart flow reserve. Purely mechanical properties of the vascular system determine the control and stability of the circulation.

Animals↗
PubMed1990

Model-based analysis of transmural vessel impedance and myocardial circulation dynamics.

The basic structure of a model of the coronary circulation has been developed to explain the relationship between transmural perfusion dynamics and intramyocardial mechanics. The model is in the form of a topologically isomorphic network representation and incorporates experimentally measured time-varying perfusion and intramyocardial pressure sources as driving inputs to the model. The intramyocardial vessels are treated as nonlinear impedance elements possessing regional external pressure-dependent resistance and capacitance. Three circuit branches, perfusing the epicardial, subepicardial, and subendocardial muscle layers, are mathematically modeled and are used to predict time-dependent flow within the left ventricular myocardium. The phasic coronary blood flow characteristics predicted by the model exhibit waveform patterns that correlate qualitatively with those patterns measured experimentally. In addition, the pressure-dependent vascular capacitance induces a sustained (out of phase with arterial inflow) venous systolic flow. The model also exhibits retrograde systolic subendocardial flow and stop-flow pressure, which are dependent on coronary resistive and capacitive properties and on the perfusion pressure decay time constant. Furthermore, the results predict an abrupt decrease in subendocardial flow with perturbation of either arteriolar or capillary bed compliance. The model describes time-dependent intramyocardial properties that have been confusing and controversial in the understanding of coronary circulation dynamics. Several steps are identified that are expected to improve and refine the model significantly.

Animals↗
PubMed1989

Autoperfusing ectothermic heart-lung preservation system.

A portable heart-lung preservation system was developed to enable distant organ procurement. In 8 dogs, a functioning heart-lung system was isolated, cannulated in situ, removed en bloc, and placed into a Plasmalyte-filled, temperature-controlled (15-38 degrees C) chamber. The perfusion circuit consisted of an adjustable-height, autologous-blood reservoir. The heart ejected through the aortic cannula with venous return (VR) into the superior vena cava. Respiration was maintained with a positive pressure ventilator. Intramyocardial tissue pressure (IMP), tissue pH, right atrial (RAP), aortic pressure (AOP), and cardiac output (CO) were monitored. Autoperfusion at normothermia and CO of 50 mL/min/kg resulted in early (3 h) deterioration of pulmonary function with progressive interstitial lung edema. Pulmonary dysfunction always preceded changes in regional myocardial contractile viability (peak IMP and d(IMP)/dt) and global function (CO, AOP). When tissue pH was regulated ectothermically (as in cold-blooded animals) (delta pH/degrees C = -0.015) the heart maintained a stable pumping mode (greater than 6 h) at myocardial temperatures of 17-28 degrees C, pH = 7.70-7.55, and heart rate of 25-50 bpm, respectively. The results indicate that a viable (greater than 6 h) autoperfused, working heart-lung system can be achieved by reducing the circulating blood flow to 30-50% of normal CO. More significantly, ectothermic alpha-stat modulation of perfusate pH and pCO2 allows a substantial reduction in organ temperature and metabolic demand without endangering induction of fibrillation and ultimate allograft failure.

Animals↗
PubMed1987

The relative buffering power of cardioplegic solutions.

Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystalloid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.

Buffers↗
PubMed1987

Operative management of coronary artery disease with poor left ventricular function.

In order to evaluate CABG in patients with depressed left ventricular function, 117 patients with an EF under 35 percent were analyzed. All patients had angina pectoris. Congestive heart failure was present in 38 percent, and one or more myocardial infarctions in 90 percent. The period of followup was up to 72 months. The hospital mortality rate was 4 percent and the late mortality rate 6 percent. Although ideal randomized trials comparing surgical and medical therapy in patients with angina and depressed left ventricular function are not available, we nevertheless believe that CABG should be available to this subset of patients. The majority of these patients will derive clinical benefit from CABG.

Adult↗
PubMed1986

Effect of fibrillation on the secretion of acetylcholinesterase from cultured embryonic rat myotubes.

We have measured acetylcholinesterase (AChE) turnover and secretion in spontaneously fibrillating rat myotubes and in cultures in which fibrillation was blocked with tetrodotoxin. The rate at which AChE appeared in the medium was 4 times greater in fibrillating than in non-fibrillating cultures. In a 2-h interval, 32% of the AChE in fibrillating myotubes and 26% of the AChE in non-fibrillating myotubes turned over. In this interval, secreted AChE accounted for 28% and 16% of the AChE turnover that occurred in fibrillating and non-fibrillating myotubes, respectively.

Acetylcholinesterase↗
PubMed1986

Assembly of monomeric acetylcholinesterase into tetrameric and asymmetric forms.

A pulse-chase experiment was performed in embryonic rat myotube cultures to examine possible precursor-product relationships among the various molecular forms of acetylcholinesterase (AChE). AChE was labeled with paraoxon, a compound which diethylphosphorylates AChE at its active site. Diethylphosphorylated (labeled) AChE is inactive but can be reactivated by treatment with 1-methyl-2-hydroxyiminomethyl-pyridinium. Thus labeled enzyme could be followed as AChE that regained activity following treatment with 1-methyl-2-hydroxyiminomethylpyridium. To selectively label monomeric AChE (the hypothesized precursor form), cultures were treated with methanesulfonylfluoride which irreversibly inactivated more than 97% of total cellular AChE. Methylsulfonylfluoride was then washed from the cultures, and they were labeled with paraoxon during a 40-55-min recovery period. AChE appearing in the cultures during this recovery period is newly synthesized and consists almost entirely (92%) of the monomeric form. Immediately and 120-130 min after labeling, cultures were subjected to a sequential extraction procedure to separate globular from asymmetric forms. Individual forms were then separated by velocity sedimentation on sucrose gradients. In our first series of experiments, we observed a 55% decrease in labeled monomers during the chase, a 36% increase in labeled tetramers, and a 36% increase in labeled asymmetric forms. In a second series of experiments focused on individual asymmetric forms, we observed a 55% decrease in labeled monomers, a 58% increase in labeled tetramers, an overall increase of 81% in labeled asymmetric forms, and a 380% increase in labeled A12 AChE. These data provide the first uniequivocal proof that complex forms of AChE are assembled from active monomeric precursors.

Acetylcholinesterase↗
PubMed1986

A model-based system for assessing ventricular chamber pressure-volume-dimension relationship: regional and global deformation.

A system has been developed for measuring and relating in a non-beating isolated canine left ventricle dynamic changes in chamber pressure, volume, diameter, regional segment length, and wall thickness. The measurement system consists of a pulsatile blood pump whose stroke-volume and frequency can be adjusted selectively. The external pump system is used as a primary means for controlling instantaneous intraventricular volume. The relationship between left ventricular volume change, intraventricular pressure, minor axis diameter, and regional dimensions were studied as a function of pump rate. In addition to the basic constitutive properties, this system provided the means for measuring and comparing regional and global pressure-strain relationship including the effect of strain rate and its relationship to viscoelastic myocardial muscle model. The dynamic relationship between global dimensions and regional dimensions, circumferential segment length, and wall thickness were also investigated. The instantaneous relationship between intraventricular pressure resulting from periodic oscillations of chamber volume, including minor equator diameter, wall thickness, and regional segment dimensions were plotted and fitted to an exponential pressure-strain model, assuming a quasi-static large deformation. The observed difference between global and regional pressure-dimension strain stiffness coefficients can be attributed in part to basic constitutive and geometric considerations and not necessarily to the complex anisotropic or heterogeneous nature of cardiac muscle properties. This methodology provides indices which appropriately characterize the regional and global left ventricular chamber deformation and stiffness.

Animals↗
PubMed1986

How cold cardioplegia and other myocardial protective modalities changed valvular surgery.

Our study was done to determine the effect of cold cardioplegic myocardial protection on valvular heart surgery. Our techniques and results utilizing crystalloid cardioplegia in 337 consecutive patients undergoing valve replacement are presented, along with a review of the present-day status of cardioplegic solutions and the importance of each component. Our hospital mortality rates of 4 percent for single valve replacement and of 7 percent for more complex procedures represent a significant improvement compared with surgical results employing previous methods of myocardial protection. We conclude that cardioplegic myocardial protection is the current method of choice in valvular heart operations. Cardioplegia still falls short of the ideal. Continued efforts are required to improve the form of intraoperative myocardial protection.

Adult↗
PubMed1985

The intramyocardial pressure: a parameter of heart contractility.

A method of monitoring was developed to directly measure the intramyocardial pressure and to objectively assess the viability and contractility of a heart allograft before it is harvested, during its period of preservation and following its implantation. Intramyocardial pressure was measured in the subendocardial and subepicardial regions using implantable solid state sensors. The data demonstrated that a normally contracting in situ heart exhibits a transmural intramyocardial pressure gradient, the systolic subendocardial pressure being consistently greater than the left ventricle and subepicardial pressures. Subendocardial pressure markedly changes during inotropic stimulation or myocardial ischemia. In three canine allografts and in an isolated, perfused and vented beating heart similar responses were observed during pharmacologic and hemodynamic testing. The intramyocardial pressure measurement proved to be relatively insensitive to preload and afterload changes provided coronary perfusion remained unaltered. Ventricular fibrillation produced an elevated and oscillating intramyocardial pressure while cardioplegic arrest reduced it to near zero. Diastolic pressure measurements were most sensitive to detect myocardial contracture ("stone" heart) during which intramyocardial pressure increased significantly. The "stone" heart exhibited persistent mechanical activity despite no visible contraction. The edematous heart's response to inotropic stimulation was reduced. Ischemia induced by inadequate perfusion was detected by a rapid drop in systolic intramyocardial pressure, preferentially affecting the endocardial region. This study establishes that the change in diastolic intramyocardial pressures in response in inotropic stimulus is a reliable indicator of myocardial contractility and viability and could be used during the procurement and preservation of the heart for transplantation.

Animals↗
PubMed1984

An interactive microcomputer-based graphics system for analysis of cardiodynamic function.

An on-line interactive, modular, menu-driven microcomputer-based data acquisition and analysis system was designed and implemented. This system includes a low-cost commercial desk-top graphics computer with a modular construction. All these operations are performed using extended BASIC "CALL" statements. The system is designed to be used in a cardiovascular research and laboratory environment where the assessment of hemodynamic and cardiodynamic function includes routine measurements of pressure and flow. In addition, the measurement of regional and global left ventricular chamber dimensions have been implemented. The modular design of the software system is "human-engineered" to enable a simple, cost effective computer system to perform physiological measurement and control. Extended BASIC language instructions provide the casual computer user with a simple yet effective means of implementing on-line data acquisition, analysis and graphic production and display.

Cardiovascular Physiological Phenomena↗
PubMed1984

The effect of spontaneous electromechanical activity on the metabolism of acetylcholinesterase in cultured embryonic rat myotubes.

We have investigated the effect of electromechanical activity on the molecular forms of acetylcholinesterase (AChE) in cultured embryonic rat myotubes. Both globular and asymmetric forms of AChE are present on the 5th day of culture when myotubes are just beginning to fibrillate. Between days 5 and 8, the 4 S (G1), 10 S (G4), and 16 S (A12) forms increase dramatically, and appreciable 12.5 S (A8) AChE appears. When fibrillation is prevented by adding tetrodotoxin on day 4, the increases in the A12 and A8 forms are prevented, and the increases in the G4 and G1 forms are significantly impaired. At 8 days, fibrillating myotubes have 19 times more A12 AChE and over 4 times more G1 and G4 enzyme than do nonfibrillating myotubes. The effect of tetrodotoxin is reversible. When tetrodotoxin is removed at 7 days, fibrillation resumes promptly, and globular and asymmetric forms recover. Light microscopic examination of fibrillating and nonfibrillating myotubes showed that tetrodotoxin does not affect the gross morphological development of the myotubes. Titration of AChE-active sites with O-ethyl-S2-diisopropyl methyl-phosphonothionate demonstrated that the increase in AChE activity associated with fibrillation is due to an increase in the number of AChE molecules present and not to an increase in the rate at which individual AChE molecules turn over acetylcholine. To evaluate AChE metabolism in fibrillating and nonfibrillating myotubes, we examined the enzyme after inactivating it with paraoxon. Paraoxon readily penetrates cells and diethylphosphorylates a serine in the active site of AChE, thereby inactivating it. The diethylphosphorylated enzyme is stable, but it can be reactivated rapidly and quantitatively with pyridine-2-aldoxime methiodide (2-PAM). After inactivating AChE with paraoxon, we simultaneously evaluated synthesis (by following the newly synthesized active AChE) and turnover (by following the 2-PAM-reactivatable AChE). Our results show that globular and asymmetric forms of AChE are both synthesized more rapidly in fibrillating than in nonfibrillating myotubes.

Acetylcholinesterase↗
PubMed1981

The surgical management of coronary artery disease with myocardial dysfunction.

The prognosis of patients with coronary artery disease and severe left ventricular dysfunction (ischemic cardiomyopathy) is grim and medical therapy has not significantly altered its course. To evaluate the results of aortocoronary saphenous vein bypass grafting in patients with ischemic cardiomyopathy, 51 consecutive patients with left ventricular ejection fractions under 0.35 were analyzed. The average ejection fraction was 0.24. All patients had angina pectoris. Clinical congestive heart failure was present in 43 percent of the patients. Ninety percent of the patients had one or more previous myocardial infarctions. Forty-seven patients had three vessel disease and four patients had two vessel disease. Twenty-one percent of the patients had critical left main coronary artery obstruction. Twelve percent of the patients had unstable angina pectoris. Two patients had recent myocardial infarction. Improvements in operative management and surgical techniques, particularly the use of cardioplegic solution for operative myocardial protection and the judicious use of the intra-aortic balloon, have been clearly beneficial. The period of followup was 6 to 33 months. The operative mortality rate was 2 percent (one patient). There have been no late deaths. Significant improvement in angina pectoris and congestive heart failure was found in over 90 percent of the patients postoperatively. Patients with severe preoperative congestive heart failure had remarkable relief of symptoms after operation. The aortocoronary saphenous vein bypass operation can be performed in patients with coronary artery disease and severe left ventricular dysfunction with a low operative mortality rate, with marked relief of angina pectoris, and with dramatic improvement in the symptoms of congestive heart failure.

Aged↗