Biomedical subjects

R Seitelberger

Publications and source records attributed to R Seitelberger.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effects of diltiazem on perioperative ischemia, arrhythmias, and myocardial function in patients undergoing elective coronary bypass grafting.

A prospective, randomized study was performed on 120 patients undergoing elective coronary bypass grafting to define the effect of the calcium channel blocker diltiazem on perioperative ischemia, arrhythmias, and myocardial function. Patients received a continuous 24-hour perioperative infusion of either diltiazem (0.1 mg/kg per hour, n = 60) or nitroglycerin (1 micrograms/kg per minute, n = 60). Perioperative monitoring included hemodynamic measurements, three-channel Holter monitoring, repeated assessment of 12-lead electrocardiograms, and analysis of ischemia-specific laboratory parameters (creatine kinase, creatine kinase-MB, and creatine kinase-MB-mass and troponin-T). Global and regional systolic function and diastolic compliance were assessed by means of transesophageal echocardiography. The two groups did not differ with respect to preoperative and operative data. Except for a significant reduction in perioperative heart rate, diltiazem had no influence on hemodynamic parameters. The number (17 +/- 9 versus 25 +/- 5, p < 0.05) and the duration (69 +/- 47 versus 104 +/- 87 minutes, p < 0.05) of transient ischemic events were significantly reduced as compared with the nitroglycerin group. In addition, peak values of all assessed laboratory parameters except creatine kinase were significantly lower in the diltiazem group. Patients treated with diltiazem had a lower incidence of perioperative atrial fibrillation (5% versus 18%, p < 0.05) and lower numbers of ventricular premature beats per hour (10 +/- 8 versus 19 +/- 22, p < 0.05) and ventricular runs per hour (5 +/- 17 versus 32 +/- 38, p < 0.05). Postoperatively, the percent fractional area of contraction and percent systolic wall thickening of the anterior wall were significantly improved in the diltiazem group but not in the nitroglycerin group. In addition, the postoperative diastolic flow/velocity ratio was significantly lower in the nitroglycerin group than in the diltiazem group (0.949 +/- 0.391 versus 1.331 +/- 0.475, p < 0.001). It is concluded that perioperative infusion of the calcium antagonist diltiazem has no adverse effect on perioperative hemodynamics and systolic myocardial function and provides potent anti-ischemic and antiarrhythmic protection in patients undergoing coronary bypass grafting.

Arrhythmias, Cardiac↗

PubMed1993

Diltiazem provides anti-ischemic and anti-arrhythmic protection in patients undergoing coronary bypass grafting.

In 91 patients undergoing elective coronary bypass grafting, the anti-ischemic and anti-arrhythmic efficacy of a 24-hour infusion of either the calcium antagonist diltiazem (0.1 mg/kg per h, n = 44) or nitroglycerin (1 micrograms/kg per min, n = 47) were compared. Myocardial ischemia was diagnosed by Holter monitoring and the repeated assessment of 12-lead ECG and serum enzyme levels and defined as a transient ischemic event, transient coronary spasm or myocardial infarction. The two groups did not differ with respect to preoperative and operative data. Postoperatively, the average heart rate and pulse pressure rate were significantly lower in the diltiazem group. The incidence of postoperative atrial fibrillation (4.5 vs 19.1%, P < 0.01), transient coronary spasm (2.3 vs 11.4%, P < 0.05) and myocardial infarction (4.5 vs 8.5%, not significant) and the frequency of ventricular premature couplets/h (12.1 +/- 4.5 vs 18.1 +/- 5.1, P < 0.05) and ventricular runs/h (2.5 +/- 0.8 vs 6.5 +/- 2.8, P < 0.05) were lower in the diltiazem as compared to the nitroglycerin group. In addition, diltiazem-treated patients had significantly lower postoperative peak values of creatine kinase-MB (19.3 +/- 11.6 vs 29.3 +/- 20.6, P < 0.05). In conclusion, perioperative infusion of diltiazem is effective in reducing the incidence and extent of arrhythmias and myocardial ischemia in patients undergoing elective coronary bypass grafting as compared to patients receiving nitroglycerin.

Arrhythmias, Cardiac↗

PubMed1993

Growth of "new" coronary vascular structures by angiogenetic growth factors.

The efficacy of the human angiogenetic heparin-binding growth factor I (HBGF-I) to initiate site-directed growth of new blood vessels from the aorta into the myocardium was studied. First, manipulated Escherichia coli bacteria, which had received the human mRNA-transcript for HBGF I into their genetic material, were cultivated. The growth factor derived was purified using heparin-Sepharose affinity chromatography. The separation and characterization of biologically active alpha- and beta-chains was carried out using high pressure liquid chromatography (HPLC) of dialyzed and lyophilized samples from the heparin-Sepharose column. One microgram HBGF I (alpha-ECGF) was bound to polytetrafluoroethylene (PTFE) sponges, precoated with collagen type I, and implanted between the aorta and the myocardium of the left ventricle in experimental rats. Twelve growth factor implants in the experimental group were compared to six controls receiving uncoated PTFE sponges for 9 weeks. Digitized computed angiography showed new blood vessels between the aorta and the myocardium in 11 of the 12 experimental animals, and retrograde coronary perfusion by these "new" vascular structures could be seen. Histology showed no specific structures in the control group (without HBGF I). In the experimental group (with HBGF I) individual vessels with highly differentiated endothelial and smooth muscle cell layers were evident. Our experiments proved the feasibility of induced, site-directed angiogenesis. It is possible to initiate in vivo growth of new "coronary" vascular structures between the aorta and the myocardium.

Animals↗

PubMed1993

New developments in the isolated working heart: a comparison of neonatal, immature, and adult rabbits after sixty minutes of ischemia in respect to hemodynamic and biochemical parameters.

Hemodynamic and biochemical changes were studied on 36 white ELCO-rabbits, seven adult older than 150 days, seven immatures between 21 and 27 days, and seven neonatals between 7 and 14 days. Five supplementary hearts of each age group served for preischemic biochemical values. Protection during 60 min of global ischemia was provided by topical cooling and selective coronary perfusion with Bretschneider cardioplegia (8 degrees C). A comparison between pre- and postischemic results showed decreases in coronary flow in the adult (p < 0.004), aortic flow (p < 0.04), cardiac output (p < 0.02), and stroke volume (p < 0.02) in the neonate. The preservation of ATP and CP was sufficient in the adult and immature myocardium, whereas a significant decrease in neonatal ATP was found (p < 0.01). According to these findings we consider immature myocardium to be more resistant against ischemia than the two other age groups. The apparatus used is a development of the conventional working heart, but combines a physiological flow-pressure relation, with instruments guaranteeing high accuracy, devices for drug application, and fits for different sizes of hearts. Therefore, this new approach promises to be of clinical relevance for investigations on the improvement of myocardial protection in both adults and children.

Adenosine Triphosphate↗

PubMed1993

Combined perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary bypass surgery.

A randomized study was performed on 70 patients undergoing elective coronary bypass surgery to examine whether the combined, perioperative, 24-hour infusion of the calcium-channel blocker nifedipine (10 micrograms/kg/h) and the beta 1-blocker metoprolol (12 micrograms/kg/h) reduces the incidence of perioperative myocardial ischemia and arrhythmias (group NM, n = 34). The control group received nifedipine only (n = 36). Repeated assessment of serum enzyme levels (CK, CK-MB) and 12-lead ECG, together with 3-channel Holter monitoring over 48 h were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and supraventricular and ventricular arrhythmias. The two groups did not significantly differ with respect to preoperative anamnestic and surgical data. No perioperative myocardial infarction was detected in either group. However, a significantly lower incidence of transient ischemic events was observed in the NM group as compared to the nifedipine group (3% versus 11%; p < 0.05). In addition, there was a tendency towards lower CK-MB levels and peak-values of CK- and CK-MB in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia (9%) and atrial flutter/fibrillation (6%) in the NM group as compared to the nifedipine group (33 and 27%, p < 0.05). In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening of the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.

Aged↗

PubMed1992

The influence of obesity on perioperative morbidity: retrospective study of 502 aortocoronary bypass operations.

The incidence of perioperative complications after coronary artery surgery was investigated by a retrospective study of all 502 patients undergoing coronary artery bypass graft (CABG) surgery in our Department between January 1st and December 31st of last year (1990). Furthermore, the influence of obesity on the early results of surgery was assessed and the effect of preoperative weight reduction on perioperative complication rates examined. Obese patients had a greater incidence of left-stem coronary artery stenosis (p less than 0.001), hyperlipidaemia (p less than 0.05), hypertension (p less than 0.05), diabetes mellitus (p less than 0.02), and were in general younger at the time of operation (57.9 +/- 8.4 vs. 60.8 +/- 8.5 years). There were no differences in the surgery performed and in operative mortality, but there were some in perioperative morbidity. Obese patients had higher rates of infection (p less than 0.02), sternal dehiscence (p less than 0.02), arrhythmias (p less than 0.02) and myocardial infarction (p less than 0.02). No significant differences were identified in obese patients with or without preoperative weight reduction, although there was a trend of better postoperative recovery and results in patients having undergone preoperative weight reduction. Analysis of our results demonstrated obesity to be an independent risk factor for perioperative complications, hospital morbidity, and length of hospitalization.

Aged↗

PubMed1992

Serum lipid peroxide levels in the course of coronary by-pass surgery.

Reperfusion of the ischemic myocardium is associated with the extension of already existing injury. Investigation of the reperfused myocardium under different conditions revealed ultrastructural changes as well as functional disturbances which were identified as free radical-mediated damage. Free radical scavengers and antioxidant agents have been shown to reduce the size of the infarct, in which a temporary regional ischemia was followed by reperfusion. Elaborately designed in vitro and animal models strongly suggest that reperfusion injury might be of clinical significance in operations involving extracorporeal circulation, as in coronary by-pass surgery. However, there is limited information on the relationship between reperfusion injury and subsequent clinical conditions. In our study, we determined lipid peroxide concentrations in timed serum samples of patients who had undergone coronary by-pass surgery. Preoperative lipid peroxide concentrations were 2.50 +/- 0.50 mumol/l. This value increased to 3.30 +/- 1.00 mumol/l after six hours and showed a second increase to 4.20 +/- 0.80 mumol/l 48 hours after the onset of reperfusion. These results suggest that postoperative increases in lipid peroxide concentrations can be of multifactorial origin and may be an indication of reperfusion injury to the myocardium. Further studies are under way to elucidate the relevance of this increase in different groups and clinical conditions.

Aged↗

PubMed1991

Immediate effects of mammary artery revascularization versus saphenous vein on global and regional myocardial function: an intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass surgery on global and regional myocardial function using the internal mammary artery (IMA) versus saphenous vein (SV) was studied intraoperatively using transesophageal echocardiography (TEE). Thirty-two patients received an IMA and 10 patients only SV. Transesophageal echocardiography was recorded before thoracotomy, 5 minutes after the end of cardiopulmonary bypass (CPB) and after chest closure. Global and regional left ventricular function were expressed as a percent of the short axis area change (%SAAC) and a percent of the fractional area change (%FAC), respectively. Segments were classified according to their baseline function as normal, %FAC greater than 40%, or dysfunctional, %FAC less than 40%. Only normal segments were considered in this study. No significant change in %SAAC in either group was observed in this study. Internal mammary artery revascularized segments showed a significant decrease in %FAC from 57 +/- 1 before thoractomy to 53 +/- 2 5 minutes after CPB, whereas SV segments showed a significant improvement in %FAC from 56 +/- 1 to 61 +/- 1. Applying strict criteria derived from intraobserver and cycle-to-cycle variability, 17% of IMA segments had deteriorated by more than 36% whereas only 4% of SV segments showed such deterioration. Conversely, 17% of SV segments showed an increase in %FAC by more than 36% and only 3% of IMA segments improved similarily. The observed changes were of short duration and had largely resolved by chest closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.

The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.

Adrenal Cortex Hormones↗

PubMed1991

Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting.

A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗

PubMed1991

[Unilateral lung transplantation as an effective therapy in primary lung emphysema].

Unilateral lung transplantation is the treatment of choice for terminal restrictive lung disease. We report about three patients with end-stage pulmonary emphysema treated by single lung transplantation. All patients are alive 3, 6 and 7 months after the operation with good quality of life. Blood gases have normalized and lung function parameters have markedly improved. We conclude, that single lung transplantation can be an effective treatment for selected patients with end-stage obstructive lung diseases in the absence of chronic infections.

Adult↗

PubMed1991

Monitoring of mononuclear cell subsets isolated from the coronary sinus and the right atrium in patients after heart allograft transplantation.

The rejection of a transplanted heart leads to an accumulation of mononuclear cells in the cardiac tissue and to reactions of the antigen-recognizing cells with the foreign tissue. Consequently, during rejections immunologic changes, such as the number of mononuclear cells and the patterns of mononuclear cell subpopulations, should be detectable by analysis of mononuclear cells from the coronary sinus of transplanted hearts. Seventy-nine endomyocardial biopsies were performed in 37 patients. Severity of graft rejection was classified by the Billingham scheme. Thirty-two biopsy specimens showed no rejection, 33 mild, and 14 moderate rejection. After endomyocardial biopsy the coronary sinus was catheterized under x-ray guidance. Heparinized blood samples were obtained from the coronary sinus and the right atrium, and mononuclear cell counts and subpopulation pattern were compared. Patients without rejection and patients with mild rejection showed no significant differences in the patterns of mononuclear cell subpopulation identified in right atrium blood. However, a significant (1.56-fold) increase of mononuclear cells was assessed in the CS blood (p less than 0.01). Moderate rejections showed a 4.2-fold augmentation of mononuclear cells in the coronary sinus (p less than 0.005) compared with nonrejections. In addition, the T-helper/inducer (CD4) percentage increased from 27.1% in the right atrium to 41.2% in the coronary sinus (p less than 0.005), natural killer cells (CD16) from 17.7% to 31.8% (p less than 0.005), and the interleukin 2 receptor-bearing cells from 6.6% to 15.3% (p less than 0.005). Percentage of pan-T cells (CD3), T-cytotoxic/suppressor cells (CD8), and monocytes (CD14) showed no statistically significant changes. These findings correlated with grading according to endomyocardial biopsy. Using the ratio of values obtained from cells of the coronary sinus and the right atrium rendered the coronary sinus immunologic monitoring independent of changes in the administered immunosuppressive regimen. The specificity of the described method was as good as that of endomyocardial biopsy. It is concluded that the discrimination of the patterns of mononuclear cell subpopulations from right atrium versus coronary sinus blood samples is highly sensitive and allows the correct diagnosis of graft rejection within 1 to 2 hours.

Antigens, CD↗

PubMed1990

Alpha-adrenergic regulation of myocardial performance in the exercising dog: evidence for both presynaptic alpha 1- and alpha 2-adrenoceptors.

New evidence supporting both presynaptic alpha 1- and alpha 2-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective alpha 1-adrenoceptor blocker prazosin (80 micrograms/kg) or the selective alpha 2-adrenoceptor blocker idazoxan (80 micrograms/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either alpha-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. beta-adrenergic blockade prevented the heart rate and contractile effects of either alpha 1- or alpha 2-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either alpha-blocker. Together, these studies provide evidence that both alpha 1- and alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.

Adrenergic alpha-Antagonists↗

PubMed1990

Mechanisms of benefit in the ischemic myocardium due to heart rate reduction.

The studies reviewed here examine the role of heart rate reduction in the beneficial effect observed following beta-adrenoceptor blockade during exercise-induced ischemia in conscious dogs. To further study the effects of heart rate reduction on regional blood flow in an ischemic bed without collateral circulation, anesthetized swine with controlled coronary perfusion were also studied. Measurements of regional myocardial blood flow (microspheres) and contractile function (sonomicrometers) during steady state exercise in dogs with chronic coronary artery stenosis indicated the existence of severe regional contractile dysfunction and subendocardial ischemia. The administration of beta-adrenoceptor blockade (1.0 mg/kg atenolol) improved regional contractile function when heart rate was reduced from 220 to 165 beats/min. Atrial pacing during exercise to prevent the bradycardia following beta-adrenoceptor blockade eliminated the improved regional function and blood flow. Thus, the beneficial effect of beta-blockade was only apparent when exercise heart rate was reduced. In anesthetized swine with constant inflow coronary perfusion, two levels of coronary hypoperfusion were examined at heart rates of 91 beats/min or 55 beats/min. Bradycardia was produced using the bradycardic agent UL-FS 49 (0.3 mg/kg). Regional contractile function and subendocardial blood flow were markedly improved at the lower heart rate for either level of reduced coronary perfusion, indicating a redistribution of blood flow towards the subendocardium. The improvement in contractile function was larger than predicted on the basis of the improvement in blood flow per min to the subendocardium. Independent relationships between regional contractile function and the subendocardial blood flow per min were observed for each heart rate. Thus, the studies in conscious exercising dogs indicated that heart rate reduction is an essential mechanism for the improvement of ischemic regional myocardial contractile function during exercise by beta-blockade. This is likely the result of the marked improvement in subendocardial blood flow per beat which accompanies the reduced heart rate; regional myocardial blood flow per beat appears to be a predictor of regional contractile function during ischemia both at rest and during exercise.

Animals↗

PubMed1990

Alpha 2-adrenergic coronary constriction in ischemic myocardium during exercise.

The effect of either selective alpha 1- or alpha 2-adrenoceptor blockade on ischemic myocardial blood flow and function was examined in beta-blocked dogs trained to run on a motor-driven treadmill. The animals were instrumented with sonomicrometers for the assessment of regional systolic wall thickening (%WTh) of the left ventricle. For drug infusion, an intracoronary catheter was implanted in the circumflex coronary artery and a hydraulic cuff was placed proximally around the artery. Following systemic beta-blockade with 0.8 mg/kg propranolol, an acute stenosis of the circumflex coronary artery inflated during exercise induced severe dysfunction in the posterior wall. Intracoronary infusion of 80 micrograms/kg of the selective alpha 2-adrenoceptor blocking agent idazoxan improved posterior wall (PW)-%WTh from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.06) and regional myocardial blood flow (radiolabelled microspheres) in the subendocardium of the posterior wall from 0.17 +/- 0.05 to 0.45 +/- 0.30 (ml/min)/g (p less than 0.05). No increases in regional blood flow and regional myocardial function were observed after infusion of the selective alpha 1-adrenoceptor blocking agent prazosin (20 micrograms/kg) under the same experimental conditions. It is concluded that during severe ischemia, significant postjunctional alpha 2-adrenoceptor mediated coronary vasoconstriction exists. Regional alpha 2-adrenoceptor blockade, but not alpha 1-adrenoceptor blockade is effective in reducing regional ischemia and dysfunction by attenuating sympathetic vasoconstriction in the conscious dog.

Adrenergic alpha-Antagonists↗

PubMed1990

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.

Blood Pressure↗

PubMed1990

Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs.

To study the effect of selective alpha 1- or alpha 2-adrenergic blockade on the myocardial contractile and chronotropic response to exercise, 29 dogs were chronically instrumented with a sonomicrometer for measuring myocardial wall thickness and a micromanometer for measuring left ventricular pressure. During treadmill exercise, either the selective alpha 1-blocker prazosin (80 micrograms/kg, n = 12) or the alpha 2-blocker idazoxan (80 micrograms/kg, n = 8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. alpha 1-Adrenoceptor blockade, like alpha 2-adrenoceptor blockade, was found to cause significant increases in systolic wall thickening, thickening velocity, heart rate, and left ventricular contractility, indicating an increase in inotropic state that was comparable to that with alpha 2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective alpha 1-blockade by using either systemic angiotensin II infusion (n = 6) or inflation of an intra-aortic balloon (n = 6) did not prevent the observed increases in wall thickening, heart rate, and left ventricular contractility. In four of the dogs treated with prazosin, the norepinephrine concentration in the coronary sinus was found to more than double after alpha 1-blockade. beta-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by alpha 1- or alpha 2-blockade. Selective alpha-adrenergic blockade during adrenergic activation by intravenous norepinephrine infusion, in contrast to exercise, had no effect on wall thickening, heart rate, or left ventricular contractility. These data indicate that selective alpha 1-adrenergic blockade, like selective alpha 2-adrenergic blockade, causes a significant augmentation of heart rate and left ventricular contractility in the dog during dynamic exercise. These data are consistent with the hypothesis that this occurs through a presynaptic disinhibition of neural norepinephrine release mediated by a prejunctional alpha 1-adrenoceptor.

Adrenergic alpha-Antagonists↗

PubMed1990

Effects of acylcarnitine transferase blockade on metabolism and function in the normally and underperfused canine myocardium.

The acylcarnitine transferase blocking agent, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (Clomoxir, INN), effectively inhibits free fatty acid oxidation, thereby decreasing myocardial oxygen consumption in the normally perfused myocardium without influencing cardiodynamic parameters. As a consequence, however, arterial free fatty acid levels increase significantly. In an acute dog model, we investigated the hypothesis that the sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate-induced decrease in myocardial oxygen consumption may also improve the energetic situation in the underperfused myocardium. Regional myocardial function was assessed by means of subendocardially inserted ultrasonic crystals, and changes in metabolism were measured regionally by means of a catheter inserted into a local myocardial vein in the underperfused area. The flow in the circumflex coronary artery was reduced on average by 53.5% followed 30 min later by an infusion of sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (dosage: 20 mg/kg over 20 min). Arterial free fatty acid levels continuously increased, whereas arterial glucose levels decreased. In accordance with the situation in the normally perfused myocardium, free fatty acid uptake and oxygen uptake were also reduced in the underperfused area. However, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate induced a further, transient increase in end-diastolic segment length and a sustained decrease in systolic shortening in the underperfused area, indicating a further deterioration in regional myocardial function. Control experiments with infusion of 9 g/l sodium chloride showed no change in the degree of regional myocardial dysfunction throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyltransferases↗