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Biomedical subjects

L Wetstein

Publications and source records attributed to L Wetstein.

At least 55 records · Page 3Linked to original sources
PubMed1985

Cardiac surgical techniques for treating intractable ventricular tachyarrhythmias.

Recurrent, sustained ventricular tachyarrhythmias unresponsive to medical therapy are associated with a one-year mortality of 70 to 85%. Patients who are susceptible to these reentrant arrhythmias usually have a history of previous myocardial infarction or chronic myocardial ischemic disease. More specifically, these patients demonstrate both anatomic and electrophysiologic derangements. Experimental work suggests that regions of non-uniform damage render the ventricle more susceptible to ventricular tachyarrhythmias; even relatively large areas of homogeneous myocardial ischemic damage may not display the same susceptibility to these arrhythmias. Surgical techniques are being devised to treat patients with ventricular tachyarrhythmias refractory to medical management. These have provided control of arrhythmias in patients whose disease was previously resistant to all medical treatment. The evolving surgical therapies presently employed share either of two pathophysiologic consequences which render them successful: the homogeneous ablation of previous heterogeneous myocardial ischemic damage or the delimiting of an arrhythmogenic focus by excluding conduction to surrounding myocardium. Finally, antitachycardia and defibrillating devices have also been developed to facilitate the management of patients not controlled satisfactorily with either conventional or investigative drugs. All physicians will need to be familiar with these devices.

Cryosurgery↗
PubMed1985

Histopathologic factors conducive to experimental ventricular tachycardia.

Ventricular tachyarrhythmia is the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of this arrhythmia remains an important clinical goal. The purpose of this study was to correlate histopathologic findings, specifically: pattern (heterogeneous versus homogeneous infarct morphology), distribution (viable epicardial and/or endocardial rim), and infarct size, with susceptibility to the initiation of sustained ventricular tachycardia employing programmed electrical stimulation in two canine models of experimental myocardial infarction. Twenty-one adult dogs were randomly divided into two groups: 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery and nine animals underwent permanent, complete occlusion of the left anterior descending coronary artery with latex embolization. With programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted, open chest, two weeks after infarction. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001). The presence of a viable epicardial rim was an extremely important variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Nonuniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than were homogeneous infarcts (p = 0.025). The presence of a large, nonuniform infarct correlated best with inducibility (p = 0.0002). Thus in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.

Animals↗
PubMed1984

Influence of site of stimulation on measurement of ventricular vulnerability in the normal and ischemic feline heart.

Site of stimulation is an important variable in the inducibility of ventricular tachycardia in both non-human animal infarction models and in humans; that is, proximity of the stimulating electrode to the site of reentry facilitates the induction of sustained arrhythmia. Whether site of stimulation is decisive in measurement of vulnerability to ventricular fibrillation (VF) during acute coronary occlusion has not been fully evaluated. We measured VF thresholds in 9 chloralose-anesthetized cats at 2 right ventricular and 3 left ventricular sites (2 endocardial, 3 intramural) before and after abrupt occlusion of the anterior descending coronary artery. VF thresholds were measured using a single stimulus of increasing intensity delivered during ventricular drive. Although VF thresholds were lower at endocardial sites, there were no significant differences in VF threshold among any of the sites tested at control. After occlusion, VF thresholds fell to a similar extent at all 5 sites tested. The percent reduction in VF threshold at any site was not influenced by the sequence of testing. VF may be precipitated from multiple sites and, unlike ventricular tachycardia, does not represent an isolated focus of arrhythmogenicity.

Animals↗
PubMed1984

Delineation of myocardial ischemia in an isolated blood-perfused rabbit heart preparation.

Isolated perfused heart preparations provide controlled conditions for the study of myocardial respiration and metabolism. Most studies utilize a hemoglobin-free perfusate which requires high arterial oxygen tension and high coronary perfusion rate. A blood-perfused rabbit heart preparation using an "assist" rabbit to maintain blood homeostasis has been developed which is suitable for respiratory, metabolic, and spectroscopic studies of myocardial function under controlled conditions. Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of blood-perfused rabbit heart was photographed to delineate areas of myocardial ischemia detectable as NADH fluorescence from reduced mitochondria. Blood reperfusion of ischemic myocardium resulted in disappearance of NADH fluorescence. Reocclusion of the coronary artery resulted in the same pattern and amplitude of NADH fluorescence.

Animals↗
PubMed1984

Evaluation of arrhythmogenicity of surgically induced endocardial versus ischemic myocardial damage.

Ventricular tachyarrhythmias are common sequelae of ischemic myocardial damage. To assess the susceptibility to sustained ventricular tachycardia in a canine model in which endocardial excision was performed, 30 adult mongrel dogs were divided into three groups and studied in an open-chest condition, anesthetized under pentobarbital anesthesia, 7 to 14 days after undergoing one of three alternative procedures: (Group A) sham-operated controls, 10 dogs; (Group B) left ventricular endocardial excision, 10 dogs; and (Group C) myocardial infarction produced by a 2-hour occlusion and subsequent reperfusion of the left anterior descending coronary artery, 10 dogs. Using programmed ventricular pacing with two extrastimuli via plunge electrodes at 10 normal sites in the distribution of the left anterior descending coronary artery in each dog, sustained ventricular tachycardia was induced in 0/10 Group A dogs at 0/100 sites and in 0/10 Group B dogs at 0/100 sites; in contrast, in Group C, 7/10 (70%, p less than 0.01) dogs had inducible sustained ventricular tachycardia and at 39/70 (56%, p less than 0.001) sites. Thus, 7 to 14 days following endocardial excision, dogs are no more susceptible to the initiation of sustained ventricular tachycardia than are sham-operated control animals. This is in contrast to dogs with chronic heterogeneous infarctions (Group C) due to coronary occlusion and reperfusion, which are highly susceptible to ventricular tachycardia initiation.

Animals↗
PubMed1983

The relationship between global myocardial ischemia, left ventricular function, myocardial redox state, and high energy phosphate profile. A phosphorous-31 nuclear magnetic resonance study.

UNLABELLED: The onset of global myocardial ischemia was related to mechanical function (intraventricular pressure), cellular redox state (NADH fluorophotography), and high energy profile (phosphorous-31 nuclear magnetic resonance). Ten rabbit hearts were excised and perfused on a modified Langendorff apparatus (37 degrees C; pO2 480 Torr). Developed pressure and positive and negative dp/dt were determined at control, 1-10, 15, 30, 45, and 60 sec of acute global ischemia. NADH fluorophotographs were taken at control, 1-10, 15, 20, 30, 60 sec, and 5, 10, and 30 min. P-31 NMR spectra in 14 guinea pig hearts under identical conditions were obtained at control, 1, 5, 10, 20, 40, and 60 min of acute global ischemia. LV contractility diminished within 1 sec (P less than 0.01) of ischemia and dropped to less than 35% of control by 1 min. Reduction of mitochondria was detected by epicardial NADH fluorophotography at 2 sec of ischemia. Cellular pH diminished 0.3 pH units by 5 min. Adenosine triphosphate (ATP) concentration remained at control levels while phosphocreatine (PCr) dropped to 63 +/- 8.5% of control by 1 min of ischemia. CONCLUSIONS: After the onset of global ischemia (1) mitochondrial electron transport ceases by 2 sec; (2) acidosis develops immediately; (3) LV contractility diminishes by 1 sec; (4) ATP concentration appears to be buffered by PCr, and is dissociated from myocardial function.

Adenosine Triphosphate↗
PubMed1983

Influence of mixed venous oxygen tension (PVO2) on blood flow to atelectatic lung.

The influence of mixed venous oxygen tension (PVO2) on blood flow to the atelectatic left lung was studied at normal and reduced cardiac outputs (CO) using extracorporeal veno-venous bypass in six pentobarbital anesthetized, mechanically ventilated dogs. Aortic and left pulmonary artery flows; airway, left atrial, central venous, pulmonary, and systemic arterial pressures; hemoglobin, arterial, and mixed venous blood gases were measured. The blood flow reduction observed in atelectasis was altered by the PVO2. Approximately 50% of blood flow was diverted away from atelectatic lung when PVO2 was low (24 +/- 2 mmHg) or normal (46 +/- 2 mmHg) (mean left lung blood flow [QL%] was 23.2 +/- 4.6% with low PVO2 and 19.0 +/- 3.4%, with normal PVO2). When PVO2 was increased to greater than 100 mmHg, diversion of blood flow away from atelectatic lung did not occur and QL% was nearly the flow expected for normoxic ventilated left lung (mean QL% = 40.4 +/- 5.9%). Shunt (QS/QT%) was significantly greater when PVO2 was high than when it was normal or low (mean QS/QT% = 51.7 +/- 5.6%, 31.0 +/- 3.1%, 26.0 +/- 3.4% with high, normal, and low PVO2, respectively). Mean PaO2 was significantly greater when PVO2 was high than when PVO2 was normal or low, despite the increase in QL% and QS/QT% (PaO2 = 327 +/- 25 mmHg, 220 +/- 32 mmHg, 115 +/- 21 mmHg with high, normal, and low PVO2, respectively). A 40% reduction in cardiac output significantly decreased transmural pulmonary artery pressure but did not affect PaO2, QS/QT%, or QL%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Surgical therapy for ventricular tachyarrhythmias.

Recurrent sustained ventricular tachyarrhythmias unresponsive to medical therapy are associated with a one year mortality of 70 to 85 per cent. Patients who are susceptible to these re-entrant arrhythmias usually have a history of previous myocardial infarction or chronic myocardial ischemic disease. More specifically, these patients demonstrate both anatomic and electrophysiologic derangements. Experimental work suggests that regions of non-uniform damage render the ventricle most susceptible to ventricular tachyarrhythmias, and even relatively large areas of homogeneous myocardial ischemic damage may not display the same susceptibility to these arrhythmias. Surgical techniques are being devised to treat patients with ventricular tachyarrhythmias refractory to medical management. These have provided control of arrhythmias in patients whose disease was previously resistant to all medical treatment. The evolving surgical therapies presently employed share either of two physiopathologic consequences which render them successful: the homogeneous ablation of previous heterogeneous myocardial ischemic damage or the delimiting of an arrhythmogenic focus by excluding conduction to surrounding myocardium. Finally, antitachycardia and defibrillating devices have also been developed to facilitate the management of patients not controlled satisfactorily with either conventional or investigative drugs. The surgeon will need to be familiar with these devices as well.

Animals↗
PubMed1982

Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart.

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.

Animals↗
PubMed1982

Platelet-mediated cardiac ischemia.

Although platelets have been associated with angina pectoris, myocardial infarction, and sudden death, the platelet's capacity for induction and propagation of cardiac ischemia remains incompletely defined. We therefore evaluated the effects of platelet activation occurring within the coronary circulation and tested the hypothesis that inhibition of platelet function would prevent platelet-induced cardiac ischemia. Human platelets were isolated from blood obtained from normal donors by Sepharose 2B column chromatography, resuspended in Hepes buffer, and added to the perfusate of a Langendorff rabbit heart (platelet counts greater than 10,000/microliters). Without, and with low dose (10 microM) prostaglandin E1 (PGE1), a reversible inhibitor of platelet function, immediate and irreversible global cardiac ischemia, as monitored by NADH fluorescent photography, ensued (N = 4) following platelet activation with thrombin (0.1 to 1 U/ml). Higher concentrations of PGE1 (0.1 to 1 mM, N = 2) or aspirin ingestion (1000 mg taken approximately 12, 4, and 1 hr prior to experiment, N = 2) completely prevented this platelet-induced myocardial ischemia. Aspirin, unlike PGE1, was effective despite its inability to block thrombin-induced platelet aggregation in our in vitro gel-filtered system. We conclude that activation of platelets within the coronary circulation is sufficient for induction of irreversible cardiac ischemia. The efficacy of aspirin, a cyclooxygenase inhibitor, further suggests that the products of arachidonate metabolism (e.g., thromboxanes) have a fundamental role in the genesis of platelet-mediated myocardial ischemia.

Animals↗
PubMed1982

Pharmacologic modification of myocardial ischemia.

The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/ml; and 10 with propranolol (P), 1 microgram/ml. Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 +/- 3 to 77.9 +/- 3 ml/min) and 150% (48.3 +/- 2 to 72.3 +/- 2 ml/min), respectively (p less than 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 +/- 4 mm2 to 110 +/- 9 mm2 between the postligation control and the end of the experiment (p less than 0.01). The ischemic area of M-treated hearts decreased from 131 +/- 5 mm2 to 113 +/- 5 mm2 (p less than 0.05). P produced no change in ischemic area (p greater than 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 +/- 13 vs 383 +/- 12 mu, p greater than 0.1). The oxygen-diffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 +/- 12 mu to 861 +/- 76 mu and 681 +/- 62 mu, respectively (p less than 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P- and H-treated hearts.

Animals↗
PubMed1982

Colo-pericardial fistula: complication of colonic interposition.

This report discusses a unique and previously unreported complication of a colonic interposition following esophageal replacement. A 7-year-old boy under-went a right colonic interposition following extensive esophageal lye burn. Fifteen years post-colonic interposition, the 22-year-old man was admitted to an adult medical ward with chest pain, cardiomegaly, and fever. Barium swallow revealed a colo-pericardial fistula with massive pericarditis. The patient survived an immediate thoracotomy with the removal of the colon and a pericardiectomy. Several months later the patient underwent a successful left colonic interposition. This case illustrates that immediate and aggressive surgical therapy may prevent an otherwise fatal outcome.

Journal Article↗
PubMed1982

Mediation of cardiac ischemia by thromboxanes released from human platelets.

We evaluated the consequences of platelet activation within the coronary circulation and determined the contribution of released thromboxanes, the most potent vasoconstrictors known, to the ensuing cardiac ischemia. Human platelets were isolated by sepharose column chromatography from blood of normal donors and added to the crystalloid perfusate of a Langendorff rabbit heart (platelet counts greater than or equal to 10,000/microliters). Following thrombin-induced (1 U/ml) platelet activation, the coronary flow decreased by 30 +/- 10% (mean +/- SEM, P less than 0.02), the mean concentration of thromboxane B2 in the coronary sinus effluent rose to 62 +/- 25 pmol/ml, and immediate, often irreversible cardiac ischemia as monitored by nicotinamide adenine dehydrogenase autofluorescence photography, ensued. However, with high concentrations of the platelet inhibitor and vasodilator, prostaglandin E1 (1.0 mM), the coronary flow increased by 50 +/-= 15%, and the epicardial fluorescence remained unchanged despite a small (10 +/- 3 pmol/ml) increase in coronary sinus thromboxanes. Platelets isolated from donors who ingested aspirin were incapable of thromboxane synthesis (less than 5 pmol/ml) but remained normally responsive to thrombin-induced activation. When these platelets were challenged by thrombin during cardiac perfusion, however, coronary flow and epicardial fluorescence remained unchanged. We conclude that platelet activation within the coronary circulation can induce irreversible cardiac ischemia, which, however, can be prevented by appropriate pharmacologic inhibition of platelet function. Furthermore, the fact that cardiac perfusion was preserved during a thrombin challenge of platelets from aspirin-treated donors establishes a fundamental role for the products of cyclooxygenase activity (e.g., thromboxanes) in the genesis of this form of myocardial ischemia.

Aspirin↗
PubMed1982

Initiation of ventricular tachyarrhythmia with programmed stimulation: sensitivity and specificity in an experimental canine model.

Programmed stimulation (PS) is used in the catheterization laboratory and operating room to initiate and study malignant ventricular tachyarrhythmia (VT). The purpose of this study was to evaluate the specificity and sensitivity of PS in short-term studies of 10 normal animals (group A), 10 sham-operated controls (group B), and 10 dogs with chronic myocardial infarction susceptible to inducible VT by an occlusion-reperfusion method (group C). Groups B and C were studied 7 to 14 days after the initial procedure. the pH, PaO2, and PaCO2 were determined and corrected every 30 minutes during the procedure. When bipolar ventricular pacing with three ventricular extrastimuli was used, VT initiation was attempted at 10 normal intramyocardial sites in groups A and B and in close proximity (less than or equal to 1 cm) to areas of infarction in group C. When one ventricular extrastimulus was used during ventricular pacing, VT was induced in dogs with chronic infarctions (3 of 10, 30%, group C). Using two extrastimuli, however, VT was inducible in 4 of 10 (40%) of group A, 6 of 10 60%) of group B, and all 10 (100%) of group C. With three extrastimuli, all 30 dogs had inducible VT. Overall, PS with one extrastimulus was highly specific in 100% but insensitive in 30%. With two extrastimuli the sensitivity increased to 100%, but the specificity fell to 50%. Finally, with three extrastimuli the sensitivity was also 100%, but the specificity decreased to 0%. PS remains an invaluable technique in diagnosing and assessing therapy for patients with VT. The diagnostic implications of this test await more precise pathophysiologic elucidation of arrhythmic mechanisms.

Animals↗