Effects of anticoagulation on recurrent systemic emboli in mitral stenosis.
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Adult↗
Biomedical subjects
H L Brooks
Publications and source records attributed to H L Brooks.
Time course of recovery of "stunned" myocardium following variable periods of ischemia in conscious and anesthetized dogs.
Persistence of regional contractile dysfunction after restoration of blood flow to transiently ischemic myocardium has been well described. To date, most studies have been performed in anesthetized animals. The present investigation compared the time course of recovery of regional segment shortening (percentage of segment shortening) in anesthetized versus conscious dogs subjected to a brief period of total occlusion of the left anterior descending coronary artery. Periods of occlusion lasting 5, 10, and 15 minutes were followed by 3 hours of reperfusion. Dogs anesthetized with sodium pentobarbital (30 mg/kg intravenously) had a significantly higher heart rate and blood pressure and lower dP/dt than conscious dogs. Coronary artery occlusion resulted in similar degrees of regional dyskinesis or akinesis, indicative of severe myocardial ischemia, in all experiments. During reperfusion, a gradual return of contractile function toward baseline was observed. At the end of the first 15 minutes of reflow, dogs subjected to 5 minutes of coronary occlusion demonstrated approximately 70% of control segment shortening in the previously ischemic zone. Animals subjected to 10- and 15-minute periods of coronary artery occlusion showed approximately 60% and 40% of control segment shortening at the same time point, respectively. The remainder of the 3-hour reperfusion period was characterized by a more gradual recovery of regional segment function. No differences were observed between anesthetized and conscious animals. It is concluded that the time course of functional recovery of postischemic reperfused myocardium is directly related to the duration of coronary occlusion and is similar in conscious and anesthetized dogs.
Anesthesia, Intravenous↗
Stimulation of myocardium during reperfusion injury by a new inotrope-vasodilator agent, MCI-154.
The systemic and coronary hemodynamic actions of a newly synthesized inotropic agent structurally related to milrinone and amrinone, MCI-154 (0.5-4.0 micrograms/kg/min IV), were studied in 2 groups of conscious, chronically instrumented dogs with normal or depressed postischemic, reperfused myocardium after a 15-min coronary artery occlusion. In an additional group of control experiments, the time course of recovery of postischemic, reperfused myocardium was studied to verify the constancy of regional segment shortening in the previously ischemic zone during the time corresponding to drug infusion. Similar inotropic actions of MCI-154 were observed in both normal and postischemic, reperfused hearts, indicating significant contractile reserve to be present in 'stunned' myocardium. Global contractility as measured by peak positive dP/dt was significantly increased in both groups. In postischemic, reperfused myocardium 90 min after initiation of reflow, regional segment function remained depressed at 44% of control but improved to 93% of control after administration of MCI-154. In addition, MCI-154 produced significant dose-related decreases in mean arterial pressure, left ventricular end-diastolic pressure, end-diastolic segment length, and diastolic coronary vascular resistance. The data demonstrate that in addition to producing beneficial hemodynamic changes, MCI-154, a new non-sympathomimetic inotropic agent, markedly enhances regional contractility of postischemic, reperfused myocardium.
Animals↗
Changes in adrenergic pressor responses by calcium channel modulation in conscious dogs.
The influence of the slow channel calcium entry blocker, nifedipine, and the slow channel calcium entry promoter, BAY-K 8644, on receptor-mediated hemodynamic responses was studied in chronically instrumented, conscious dogs. Following ganglionic, cholinergic, and beta-adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg iv), a selective alpha 1-adrenoceptor agonist, and B-HT 933 (20 micrograms/kg iv), a selective alpha 2-adrenoceptor agonist, as well as a nonadrenergic vasoconstrictor, vasopressin (0.003 IU/kg) were administered before and after infusions of nifedipine or BAY-K 8644 (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X min-1). In doses producing minimal or no haemodynamic effects, nifedipine caused dose-related attenuation from control of phenylephrine- (from 26 +/- 3 to 8 +/- 1 mmHg), B-HT 933- (from 30 +/- 2 to 5 +/- 2 mmHg), and vasopressin- (24 +/- 1 to 2 +/- 2 mmHg) mediated changes in mean arterial pressure. In contrast, BAY-K 8644 produced dose-related potentiation from control of the same pressor responses (phenylephrine, 24 +/- 2 to 41 +/- 3 mmHg; B-HT 933, 28 +/- 3 to 46 +/- 2 mmHg; vasopressin, 25 +/- 3 to 45 +/- 5 mmHg). In addition, BAY-K 8644 produced a marked increase in the duration of the pressor response produced by all three agonists. Thus, in conscious dogs, alpha 1-, alpha 2-, and vasopressin-mediated pressor responses are strongly modulated by transmembrane calcium flux and can be influenced by dihydropyridine slow channel calcium agonists and antagonists.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Differential effects of nifedipine, nicorandil and nitroglycerin on the pressor responses elicited by selective alpha-1 and alpha-adrenoceptor agonists in conscious dogs.
The influence of vasodilators with varying mechanisms of action on pressor responses mediated by alpha-1 and alpha-2 adrenoceptors was investigated in chronically instrumented, conscious dogs. After ganglionic, cholinergic and beta adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg i.v.), a selective alpha-1 adrenoceptor agonist, and B-HT 933 (20 micrograms/kg i.v.) a selective alpha-2 adrenoceptor agonist, were administered before and in the presence of infusions of nifedipine (0.25-2.0 micrograms/kg/min), nicorandil (4.0-32.0 micrograms/kg/min) or nitroglycerin (1.0-8.0 micrograms/kg/min). Nifedipine produced a dose-related attenuation of the increase in mean arterial pressure after bolus administration of phenylephrine (from 26 +/- 1 to 7 +/- 1 mm Hg) and B-HT 933 (from 29 +/- 2 to 5 +/- 1 mm Hg). Nicorandil did not affect phenylephrine-mediated pressor responses but significantly attenuated those to B-HT 933 (28 +/- 2 to 10 +/- 1 mm Hg). In contrast, nitroglycerin had no effect on either phenylephrine or B-HT 933-mediated responses. In additional experiments after autonomic nervous system blockade, multiple doses of phenylephrine (0.6, 1.25 and 2.5 micrograms/kg i.v.) and B-HT 933 (10, 20 and 40 micrograms/kg i.v.) were administered before and after i.v. infusions of nifedipine (1.0 microgram/kg/min) or nicorandil (16.0 micrograms/kg/min). Nifedipine significantly decreased the pressor responses to all doses of phenylephrine and B-HT 933. In contrast, the attenuation from control of alpha-2-mediated increases in arterial pressure by nicorandil was partially overcome at higher doses (40 micrograms/kg) of B-HT 933.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Agonists↗
Usefulness of right ventricular diastolic collapse in diagnosing cardiac tamponade and comparison to pulsus paradoxus.
To compare the sensitivity, specificity and predictive value of right ventricular (RV) diastolic collapse and pulsus paradoxus as signs of cardiac tamponade, 21 consecutive patients with pericardial effusion and suspected cardiac tamponade underwent prospective hemodynamic and echocardiographic evaluation. Simultaneous hemodynamic and echocardiographic data were obtained in all patients before and after pericardiocentesis. Cardiac tamponade was considered present when there was diastolic equilibration of the intrapericardial, right atrial and pulmonary capillary wedge pressures and elevation of these pressures to more than 10 mm Hg. RV diastolic collapse was 93% sensitive and 100% specific in diagnosing cardiac tamponade, whereas pulsus paradoxus was only 79% sensitive and 40% specific. The positive and negative predictive values of RV diastolic collapse (100% and 83%) were considerably better than pulsus paradoxus (81% and 40%) and demonstrate that RV diastolic collapse is more sensitive, specific and predictive of cardiac tamponade than is pulsus paradoxus. Serial simultaneous hemodynamic and echocardiographic observations at multiple points during pericardiocentesis in a smaller subgroup (5 patients) also suggest that the hemodynamic effects of RV diastolic collapse in cardiac tamponade are mediated by an increase in intrapericardial pressure.
Adult↗
Recovery of contractile function in post-ischaemic reperfused myocardium of conscious dogs: influence of nicorandil, a new antianginal agent.
The effects of intravenous administration of nicorandil, a new antianginal agent, on the recovery of regional myocardial contractile function after a 10 minute coronary artery occlusion were studied in chronically instrumented conscious dogs. Compared with the control group nicorandil administration resulted in an increase in heart rate and a decrease in blood pressure with an overall increase in the double product during the preocclusion period, no significant difference in double product during ischaemia, and a significant decrease in double product during reperfusion. After reperfusion the return of regional contractile function was appreciably enhanced in the nicorandil treated group. These effects were seen immediately after coronary reflow and persisted throughout the reperfusion period. These data suggest that nicorandil protects ischaemic cardiac tissue, and that the beneficial actions may be mediated through a reduction in left ventricular afterload.
Animals↗
Importance of retrograde coronary flow in the prediction of experimental myocardial infarct size.
The relationship between myocardial infarct size (measured by a histochemical stain) and coronary collateral blood flow (measured via retrograde flow and by use of radioactive microspheres) was studied in anesthetized dogs with high, moderate and low retrograde flows undergoing a 2-hour occlusion and 30-min reperfusion of the left anterior descending coronary artery. The results demonstrate that experimental myocardial infarct size is closely related to native coronary collateral blood flow, and the large variability in collateral perfusion amongst dogs is a source of variability in the mass of myocardium undergoing irreversible damage following acute coronary occlusion. Results also demonstrate that the variability in experimental infarct size can be reduced and ultimate infarct size predicted prior to irreversible tissue injury by initial measurement of retrograde coronary blood flow.
Animals↗
Slow channel calcium activators, a new group of pharmacological agents.
Specific calcium channels in myocardium and vascular smooth muscle and pharmacologic agents which possess the ability to block them have been the subject of intense research over the past several years. Many studies have utilized dihydropyridine derivatives (e.g. nifedipine, nitrendipine, nisoldipine) which have been shown to be efficacious inhibitors of calcium influx through voltage sensitive slow channels. Administration of these agents results in vascular smooth muscle relaxation and negative inotropic effects. Recently, novel dihydropyridines such as Bay k 8644, CGP 28 392 and YC-170, with actions diametrically opposed to those of compounds typified by nifedipine have been synthesized. These agents demonstrate vaso-constrictor and positive inotropic effects - actions which might be expected of compounds capable of stimulating the transmembrane influx of calcium into vascular smooth muscle and myocardium. Actions of Bay k 8644 and CGP 28 392 studied in vitro and in vivo have also shown that pharmacological blockade of beta or alpha adrenergic receptors does not influence the direct effects of these agents. Future analogs, with similar but more selective actions on myocardial calcium channels, may prove useful in the management of pathologic states characterized by insufficient contractile function of the heart.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Long-term follow-up of survivors of prehospital sudden cardiac death treated with coronary bypass surgery.
Although coronary artery bypass surgery is beneficial to patients with severe coronary artery disease, its role in preventing the recurrence of prehospital cardiac arrest in patients is not clear. In this article, we report on the long-term follow-up of 49 survivors of prehospital coronary arrest who had coronary artery bypass surgery. Prior to their prehospital cardiac arrest, 14% of the patients had a history of unstable angina. Coronary angiograms obtained after prehospital cardiac arrest showed that 71% of the patients had three-vessel coronary artery disease and 6% had single-vessel disease. The mean left ventricular ejection fraction was 45%. There were four postoperative deaths; three were caused by pump failure, and one was caused by refractory ventricular arrhythmias. After a maximum follow-up period of 102 months (mean of 55.4 months), there were seven cardiac deaths; five of the patients died of recurrent ventricular fibrillation, and two patients' deaths were related to refractory heart failure. Actuarial analyses of the 49 patients showed that the probability of survival at 6 months, 1 year, 2 years, 3 years, and 5 years was 92%, 92%, 89%, 82%, and 72%, respectively. After surgery, 35 of the 45 patients who were discharged from the hospital were asymptomatic, and 23 of the 32 patients who were employed when their prehospital cardiac arrest occurred returned to their employment. We concluded that coronary artery bypass surgery is beneficial to certain survivors of prehospital sudden death. After surgery, most patients are asymptomatic and capable of returning to their employment and the recurrence of prehospital sudden death is low.
Aged↗
Evaluation of a percutaneous catheter technique for ablation of ventricular tachycardia in a canine model.
Catheter ablation of arrhythmias is a promising new technique. The consequence of high-energy discharges in the right ventricle were investigated in a canine model of inducible ventricular tachycardia. Seventeen dogs were studied. Four served as controls while 13 underwent thoracotomy with right coronary artery ligation. Three animals died suddenly postoperatively. Programmed stimulation was performed 4 days later using a pervenous right ventricular electrode catheter. No control dog had inducible ventricular tachycardia. Eight of the experimental animals had inducible ventricular tachycardia and underwent catheter mapping. The earliest endocardial site during tachycardia was located in four dogs with monomorphic ventricular tachycardia. These sites received one or more 300 J transcatheter stored charges from a defibrillator, and at least temporary ablation was accomplished in each case. Five animals had inducible polymorphic ventricular tachycardia which could not be mapped. The endocardial electrogram amplitude decreased 55 +/- 7% (p less than 0.001) and the pacing threshold increased from 0.7 +/- 0.1 mA to 7.9 +/- 1.7 mA (p less than 0.001) after the shocks. Five of the discharges caused ventricular tachycardia or fibrillation. Autopsy revealed discrete transmural wedge-shaped necrosis without perforation. Thus when monomorphic tachycardia was induced, mapping and ablation were feasible. Transcatheter 300 J discharges produced only localized damage but had a propensity to initiate ventricular arrhythmias.
Animals↗
Mitral valve prolapse requiring surgery. Clinical and pathologic study.
The clinical, hemodynamic, surgical, and pathologic findings in 30 patients who required mitral valvular surgery and who had a preoperative diagnosis of mitral valve prolapse were reviewed. The mean age of the patients was 59.5 years; 28 patients were over 45 years of age and 10 were over 60 years. Surprisingly, 20 were males. A long history of systolic murmur was common, whereas symptoms of heart failure were of abrupt onset. At the time of surgery, a local holosystolic murmur typical of mitral regurgitation was present, although a mid- to late systolic click was not heard in any of the patients. Electrocardiographic abnormalities were present in all patients, with 13 patients demonstrating atrial fibrillation. Only four patients had a normal heart size radiographically. Echocardiography confirmed the radiographic findings, in that 27 patients demonstrated left atrial and ventricular enlargement. All 29 patients undergoing cardiac catheterization and angiography demonstrated a prolapsing mitral valve with severe regurgitation. Surgical and pathologic examination revealed findings characteristic of a myxomatous valve in all patients, with 19 also demonstrating ruptured chordae tendineae. This study demonstrates that heart failure requiring valvular surgery occurs in a subset of patients with mitral valve prolapse. In this subset, males predominate and most are over 50 years of age. These patients may be asymptomatic for many years, demonstrating mild to moderate mitral valvular regurgitation, before heart failure develops.
Adult↗
Alterations in intravascular volume affect the relation between right ventricular diastolic collapse and the hemodynamic severity of cardiac tamponade.
Right ventricular diastolic collapse has been demonstrated to be a sensitive and specific sign of cardiac tamponade. Because the shape and position of the right ventricular wall are related to the relative pressures within the pericardial space and the right ventricular chamber, the usefulness of right ventricular diastolic collapse as a marker of cardiac tamponade may be influenced by intravascular volume and right heart filling pressures. This study was undertaken to determine the effects of volume loading and hemorrhage on the point within the hemodynamic progression of cardiac tamponade at which right ventricular diastolic collapse first appears. Five unanesthetized, chronically instrumented dogs were studied with two-dimensional echocardiography during 41 episodes of cardiac tamponade induced by the intrapericardial infusion of warm saline solution. Intravascular volume was adjusted before cardiac tamponade to a hypovolemic, euvolemic or hypervolemic state using saline solution and dextran infusion or hemorrhaging to achieve the prescribed mean right atrial blood pressure. The measurements recorded during each episode of cardiac tamponade were right atrial blood pressure, aortic blood pressure, cardiac output (by electromagnetic flow meter), heart rate and intrapericardial pressure. When compared with the euvolemic state, the onset of right ventricular diastolic collapse in volume contraction occurred at a lower intrapericardial pressure (with a lower aortic blood pressure and cardiac output), whereas in volume expansion it occurred at a higher intrapericardial pressure (with a higher aortic blood pressure and cardiac output). Volume expansion delayed the decrease in hemodynamic variables during cardiac tamponade in this canine model.
Animals↗
The relative merits of pulsus paradoxus and right ventricular diastolic collapse in the early detection of cardiac tamponade: an experimental echocardiographic study.
An inspiratory decline in systolic arterial blood pressure exceeding 10 mm Hg has been used clinically to identify hemodynamically significant pericardial effusions. Recently, the echocardiographic sign of right ventricular diastolic collapse (RVDC) has been shown to occur early in the course of cardiac tamponade in association with a hemodynamically important decline in cardiac output. This study was undertaken to compare the relative merits of pulsus paradoxus and the onset of RVDC in the early detection of cardiac tamponade in an unanesthetized canine preparation. We studied six chronically instrumented, conscious dogs with two-dimensional echocardiography during cardiac tamponade induced by continuous infusion of saline into the pericardial space. We recorded intrapericardial pressure, cardiac output (electromagnetic flowmeter), aortic (catheter-tip transducer) and right atrial blood pressures, heart rate, and respiration. None of the dogs had RVDC when the pericardial space was empty, but all dogs showed RVDC during cardiac tamponade. We found that RVDC was strongly related to all of the cardiac parameters evaluated (intrapericardial pressure, cardiac output, aortic blood pressure, heart rate, and stroke volume) and provided information on each that was independent of that provided by pulsus paradoxus. Furthermore, RVDC appeared to be more strongly related to most cardiac parameters than was pulsus paradoxus and to be more sensitive and specific than pulsus paradoxus in detecting changes in intrapericardial pressure early in cardiac tamponade.
Animals↗
Effects of intravascular volume state on the value of pulsus paradoxus and right ventricular diastolic collapse in predicting cardiac tamponade.
Both pulsus paradoxus and right ventricular diastolic collapse detected by two-dimensional echocardiography are noninvasive markers of impaired cardiac function in cardiac tamponade, yet the reliability of each may vary with the patient's state of hydration. To examine the relative value of these noninvasive markers at various states of hydration, we studied five chronically prepared, conscious mongrel dogs during 37 episodes of cardiac tamponade at three different intravascular volumes. We continuously measured cardiac output (electromagnetic flowmeter), aortic blood pressure, right atrial blood pressure, intrapericardial pressure, and respirations. Intravascular volume was varied by adjusting the mean right atrial blood pressure to hypovolemic (-2 to -6 mm Hg), euvolemic (0 to 4 mm Hg), or hypervolemic (6 to 10 mm Hg) levels. The sensitivity and specificity of right ventricular diastolic collapse in predicting increases in intrapericardial pressure remained high at all levels of hydration. Pulsus paradoxus showed good sensitivity and specificity at low intravascular volumes, but both sensitivity and specificity declined at higher intravascular volumes. Thus right ventricular diastolic collapse was more sensitive and more specific than pulsus paradoxus in detecting increases in intrapericardial pressure during euvolemia and hypervolemia whereas the two tests were equally valuable in hypovolemic states.
Animals↗
The association of smoking with cardiomyopathy.
We investigated the possibility that smoking has an association with ventricular wall-motion abnormalities that is independent of its known association with coronary occlusion. We studied 4763 men between the ages of 35 and 74 who had diagnostic coronary angiography and ventriculography. We considered three kinds of wall-motion abnormalities: hypokinesis in one to four ventricular segments, hypokinesis in five to six ventricular segments (diffuse hypokinesis), and akinetic or dyskinetic wall motion in at least one segment. Among men younger than 55, the relative risk of diffuse hypokinesis was 2.78 (1.1 to 6.99) for heavy smokers as compared with nonsmokers. Adjusting for the degree of coronary occlusion or eliminating subjects with a history of myocardial infarction did not change this relative risk. Among men who were 55 or older the relative risk (odds ratio for heavy smokers as compared with nonsmokers) was not significant (0.55 to 2.28). Regardless of age the relative risk of akinesis or dyskinesis, adjusted for coronary stenosis, was significant: 1.84 (1.28 to 2.65) for men under 55 and 1.57 (1.12 to 2.19) for men 55 or older. These results suggest that smoking is related to both cardiomyopathy and transmural myocardial infarction and that the relationships are largely separate from the association of smoking with coronary stenosis.
Adult↗
Orbital Burkitt's lymphoma in a homosexual man with acquired immune deficiency.
A 22-year-old homosexual man had persistent systemic lymphadenopathy and a three-week history of rapid swelling and induration of his right upper eyelid. Acquired immune deficiency leading to the development of lymphoma was suspected. A biopsy specimen of the mass revealed Burkitt's lymphoma and treatment with systemic chemotherapy and radiation therapy resulted in remission. A significant number of patients with acquired immune deficiency are developing Burkitt's lymphoma. The three separate syndromes of acquired immune deficiency and their associated ophthalmic manifestations are discussed.
Acquired Immunodeficiency Syndrome↗
Operative approach to endocarditis.
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Adult↗