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Biomedical subjects

H R Zerkowski

Publications and source records attributed to H R Zerkowski.

At least 73 records · Page 4Linked to original sources
PubMed1997

Time course of high-intensity transient signals in patients undergoing elective heart valve replacement: a prospective study.

BACKGROUND AND AIMS OF THE STUDY: This study was performed to evaluate the time course of intracranial high-intensity transient signals (HITS) in patients undergoing elective heart valve replacement. METHODS: Thirty-three patients were enrolled in this study. The examination protocol included serial (before and at one, five, 90 and 180 days after surgery) monitoring sessions with transcranial Doppler and detailed neurological examination. Monitoring was performed bilaterally over the middle cerebral arteries for one hour per session using 2 MHz probes. Microembolic signals were recognized according to standard criteria and stored on a computer for later evaluation. RESULTS: HITS prevalence increased from 3% preoperatively to 41% on the first postoperative day and remained unchanged during the postoperative period. No influence of the intensity of anticoagulation or valve type on HITS counts was evident. Unilateral monitoring provided adequate results in 83.9% of cases. CONCLUSIONS: The causative role of the valve implant in the pathogenesis of HITS appears certain, since their prevalence dramatically increases following valve implantation. Valve type, duration of valve implant or intensity of anticoagulation did not influence HITS counts. Bilateral monitoring is warranted for accurate evaluation of HITS counts in this patient group.

Aortic Valve↗
PubMed1996

Timing of surgery in patients with acute infective endocarditis.

OBJECTIVE: Surgical intervention in patients with active infective endocarditis is generally considered as indicated in few high-risk patients who have developed severe complications such as heart failure, persistent septicemia or recurrent arterial embolism, but the question of when to intervene is still subject to discussion. EXPERIMENTAL DESIGN: Retrospective study. SETTING: Cardio-Thoracic Surgery Unit, University clinic. PATIENTS, INTERVENTIONS AND RESULTS: From 1984 to 1994, 130 patients (87 male, mean age 43.2 +/- 12.7 years) underwent heart valve replacement or reconstruction for infective endocarditis of native or prosthetic valves. 89 of them had acute infection requiring urgent surgical treatment. Over-all operative mortality was 12.3%. Certain preoperative factors were investigated regarding their influence on postoperative death. Statistical analysis revealed functional class according to NYHA as well as extravalvular involvement of the infection as significant risk factors or mortality. Emergency operation was not significantly associated with increased operative mortality, neither were the causative organism, a history of arterial embolism or persistent septicemia. CONCLUSIONS: In active infective endocarditis the optimal time to perform surgery is before the onset of severe end-stage heart failure or spread of the infection to extravalvular tissue. If one of these complications is imminent, urgent intervention is indicated.

Acute Disease↗
PubMed1996

Impact of the incubation medium on the endothelium of autologous vein grafts: damage scoring by scanning electron microscopy.

The aim of this study was to examine the influence of different incubation media on the morphology of the endothelium of great saphenous vein grafts and establish a suitable scoring system for the evaluation of damage caused by these media. Fifty specimens of saphenous veins from ten patients during elective aorto-coronary bypass surgery were used. Ten specimens served as controls; the others were assigned to test groups and exposed to heparinized whole blood, Bretschneider's HTK, human albumin or Ringer's solution. Specimens exposed to heparinized blood showed only slight morphological alterations, whereas the other three mediums caused severe damage. Thus, heparinized blood seems to be most suitable as a rinsing and incubation medium. A widely accepted scoring system for the quantification of endothelial damage caused by the incubation media did not adequately reflect the morphology alterations in the cytoskeleton and membrane topology. The proposed scoring system, which is based on endothelial cell separation, endothelial cell loss, amount of deposits, endothelial cell surface homogeneity, in addition to the frequency of spikes and blebs, seems to be suitable for characterizing differences in endothelial morphology.

Adult↗
PubMed1995

Regression of pre-existing coronary artery disease in a donor heart after cardiac transplantation.

This report is about the angiographic follow-up, over 5 years, in a patient with urgent heart transplantation grafted with an atherosclerotic donor heart because of severe congestive heart failure due to dilative cardiomyopathy. Sequential quantitative angiography documented a regression of the luminal narrowing of a focal lesion in the right coronary artery with a minimal luminal diameter of 1.38 mm (56% diameter stenosis) in 1988 to 2.78 mm (13%) in 1993. During this catheterization in 1993 intravascular ultrasound imaging illustrated almost no atherosclerotic vessel wall abnormalities at the site of the previous angiographic luminal narrowing as well as in the adjacent segments. These findings might promote the potential acceptance of heart transplant donors with a certain extent of coronary artery disease in the case of urgent organ request, if close follow-up and strict guidance of the patient by the transplanting team is feasible.

Adolescent↗
PubMed1995

Age-dependent changes in the beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in human right atrium.

With increasing age, cardiac beta-adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in right atrial appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9; group C, > 50 years, mean age 66.1 +/- 1.5 years, n = 23) without apparent heart failure who were undergoing open heart surgery beta-adrenoceptor number and subtype distribution (by (-)-[125I]-iodocyanopindolol [ICYP] binding), adenylyl cyclase activity, and Gs- and Gi-protein alpha-subunits (by quantitative Western blotting). beta-Adrenoceptor number in the three groups was not significantly different; in contrast, basal, 10 microM GTP-, 100 microM isoprenaline (ISO), 10 mM NaF-, 100 microM forskolin-, and 10 mM Mn(2+)-stimulated adenylyl cyclase activity was significantly higher in group A than in group B and was further decreased in group C. Similarly, 100 microM terbutaline-, 100 microM histamine-, and 100 microM 5-HT-stimulated adenylyl cyclase activity significantly decreased from group A to group C. Moreover, all these adenylyl cyclase parameters were significantly negatively correlated with the age of the patients. Although Gs alpha was not altered, Gi alpha in group C was significantly higher than in group A; moreover, there was a weak but significant positive correlation between Gi alpha and the age of the patients. We conclude that an impairment of the activity of the catalytic unit of adenylyl cyclase is involved in the decrease in cardiac beta-adrenoceptor function with age; an increase in Gi alpha might contribute further to the reduced beta-adrenoceptor function.

Adenylyl Cyclases↗
PubMed1994

Positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in the human heart: effects of long-term beta 1-adrenoceptor antagonist treatment.

OBJECTIVES: This study was conducted to determine whether activation of cardiac beta 2-adrenoceptors increases contractility in humans and whether this is affected by long-term beta 1-adrenoceptor antagonist treatment. BACKGROUND: Coexistence of beta 1- and beta 2-adrenoceptors in the human heart is generally accepted. The functional importance of cardiac beta 2-adrenoceptors for increases in contractility in humans, however, has not been completely established. METHODS: We studied 1) the beta-adrenoceptor subtype mediating positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in vitro (on right atrial and left ventricular preparations from nonfailing human hearts) and increases in contractility (by measurement of systolic time intervals) in vivo in seven healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers with the beta 1-adrenoceptor antagonist bisoprolol affects terbutaline-induced increases in contractility. RESULTS: In vitro terbutaline caused a concentration-dependent increase in atrial and ventricular adenylate cyclase activity and force of contraction. Terbutaline effects were antagonized only by the beta 2-adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta 2-adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased heart rate and shortened the pre-ejection period and heart rate-corrected electromechanical systole (QS2) time. These effects are mediated predominantly by beta 2-adrenoceptor stimulation because they were only marginally affected by the beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg orally), either given 2 h before infusion or long term for 3 weeks. CONCLUSIONS: Stimulation of cardiac beta 2-adrenoceptors in humans causes not only in vitro but also in vivo positive inotropic effects. Long-term beta 1-adrenoceptor antagonist treatment does not considerably affect beta 2-adrenoceptor-mediated in vivo increases in contractility. Thus, it may be possible to treat patients with chronic heart failure and long-term beta 1-adrenoceptor antagonist therapy with beta 2-adrenoceptor agonists if immediate inotropic support is needed.

Adenylyl Cyclases↗
PubMed1994

Diagnosis and therapeutic consequences of intramural aortic hematoma.

The classical triad of sudden devastating chest pain, electrocardiographic absence of acute myocardial infarction, and identification of an upstream flap in the ascending aorta by transesophageal echocardiography (TEE) indicates aortic type A dissection requiring emergent surgery. Among 34 patients presenting with clinical signs and symptoms of an aortic dissection, three did not show the mandatory flap in the upstream aorta. The only echocardiographic finding was aortic wall thickening indicating an intramural hematoma. Two of these patients showed early aortic ectasia and one showed a pericardial effusion. Despite the missing flap echocardiographically, surgery was performed in all three patients. The surgical approach was the same as that for patients with a type A dissection. Two patients are doing well after the procedure, and one patient died after reoperation. The postoperative histologic work-up confirmed that there was no intimal tear or dissection of the intimal layer. We conclude that the echocardiographic finding of an intramural hematoma combined with typical clinical signs of chest pain, with myocardial infarction ruled out, requires emergent surgical intervention.

Adult↗
PubMed1994

The effects of beta-adrenoreceptor blockade on oxygen consumption during cardiopulmonary bypass.

The effect of chronic beta-adrenoreceptor blockade (beta-blockade) on hemodynamics and oxygen consumption (VO2) during cardiopulmonary bypass (CPB) in mild hypothermia (34 degrees C) was studied in 34 patients. The study group included 17 patients who received beta-adrenergic blocking drugs for at least 1 mo prior to the study. Seventeen patients who did not receive beta-adrenergic blockers served as controls. Demographic data in the two groups were comparable. Prior to induction of anesthesia, the heart rate was slower in the beta-adrenergic blocker group as compared to the control group. During CPB, measurements were made at two pump flow rates: 2.4 L.min-1.m-2 and 3.0 L.min-1.m-2. Oxygen delivery was similar in the two groups (beta-adrenergic blocker vs control) but the oxygen consumption was significantly lower in the beta-adrenergic blocker group as compared to the control group at both flow rates (P = 0.009). Increasing the flow rate from 2.4 L.min-1.m-2 to 3.0 L.min-1.m-2 produced a similar increase (P = 0.0001) in oxygen consumption in both groups. Increasing flow rate increased mean arterial pressure (MAP) and central venous pressure (CVP) and decreased systemic vascular resistance index (SVRI) and reservoir volume similarly in both groups. Thus, compared to the control group, patients on chronic beta-adrenergic blocker medication have a lower VO2 during CPB.

Adrenergic beta-Antagonists↗
PubMed1994

Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of adenylate cyclase in human right atrium.

To study signal transduction pathways of endothelin (ET) in human heart, we assessed, in isolated human right atria, the effects of ET-1 and ET-3 on inositol phosphate (IP) formation and on the adenylate cyclase/cyclic AMP system. In right atrial slices, ET-1 (10(-10)-10(-6)M) concentration-dependently increased [3H]IP accumulation and decreased 10-microM isoprenaline-induced or 1-microM forskolin-induced increases in cyclic AMP content. ET-3 was approximately 100 times less potent. The cyclic AMP-decreasing effect of ET-1 (10(-11)-10(-6)M) could also be demonstrated directly in adenylate cyclase assays in right atrial membranes; again, ET-3 was approximately 100 times less potent. We conclude that in human right atrium, ETA receptors couple to two different signal-transduction pathways: IP formation and inhibition of adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Results of mitral valve reconstruction in mitral valve insufficiency.

In the last three years forty mitral valve reconstruction (MR) procedures were performed in case of mitral insufficiency (MI). In three cases, anatomical changes made reconstruction impossible for us. One patient had to be re-operated because of unsatisfactory valve function. There was no operative mortality. In twelve of the patients, mitral insufficiency was the only problem, while in twenty eight others additional cardiac procedures (CABG, AVR) were performed. The patients' age ranged from 17 to 77 years. The aortic cross-clamping time for mitral reconstruction without additional cardiac procedures ranged from 35 to 134 minutes. With one exception, the post-operative TEE indicated no, or very little, insufficiency. We concluded that the mitral valve insufficiency can be corrected with very good results and with a very low rate of complications. Such corrections ought therefore be taken into consideration before valve replacement.

Adolescent↗
PubMed1994

[Concept for therapy of heart failure in heart surgery].

Perioperative deterioration of the circulatory performance of patients undergoing heart surgery ranges from transitory impairment in cardiac output by deterioration of the compensation range of the oxygen transport system to manifest circulatory failure without previous myocardial damage and the acute decompensation of pre-existing chronic heart failure. On the basis of the current state of knowledge in this field, a concept for rational staged treatment should be based on the different myocardial beta-adrenoceptor conditions related to the type and stage of the individual underlying heart disease and on adrenoceptor subtype specific properties of positive inotropic drugs. 1. The therapy of perioperative "circulatory" insufficiency after extra-corporal circulation consists of the use of drugs to adapt the performance of the oxygen transport system to increased overall oxygen demand. Simultaneous volume loading (by CVP) and positive inotropic support with dobutamine are the best means of treating this (normally transitory) dysregulation. 2. In the case of manifest severe circulatory insufficiency (low cardiac output syndrome), sepsis or acute heart failure (e.g., following acute myocardial infarction), the use of a pulmonary artery catheter for determining perioperative cardiac output and resistance is essential. In such cases, positive inotropic therapy is based on catecholamines of medium (dobutamine) to high (adrenaline) efficacy, because it can be assumed that the beta-adrenoceptor pattern will remain normal with regular functioning and regulation of the (remaining) myocardium up to the onset of acute heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMed1993

Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium.

The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure. All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan). We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to beta-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the beta-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.

Adenylyl Cyclases↗
PubMed1993

Sequential bilateral lung transplantation for pulmonary alveolar microlithiasis.

Lung transplantation has been successfully used in the treatment of patients with end-stage pulmonary disease and adequate cardiac function. We report about a 32-year-old man with pulmonary alveolar microlithiasis who underwent sequential bilateral lung transplantation. Preoperative hemodynamic studies revealed severe pulmonary hypertension; the right ventricular ejection fraction was 0.27. Eighteen months postoperatively, he continues to do well with normalized pulmonary and cardiac function and without clinical or histopathologic signs of graft rejection.

Adult↗
PubMed1993

Endothelial damage of the venous graft in CABG. Influence of solutions used for storage and rinsing on endothelial function.

A significant proportion of early graft occlusions after aortocoronary revascularization using autologous saphenous vein grafts (SVG) are due to mechanical and/or metabolic or biochemical endothelial lesions. The morphological examination of the endothelium, usually carried out using light microscopy or by various types of scanning electron microscopy (SEM), does not give any indication of the functioning of the endothelium (E). Functionally intact E is capable of producing endothelium-derived relaxing factor (EDRF); a practicable in vitro test is the relaxation of pre-contracted vein segments (VS) in response to acetylcholine (ACh) application. To study the effect of the solution used to rinse and store the SVG between removal and implantation on the functional characteristics of the E, we performed in vitro tests on macroscopically intact VS removed from the saphenous vein of 30 male patients who underwent elective CABG surgery. Isolated VS rings were incubated for 60 min in heparinized whole blood (HWB), Bretschneider's cardioplegic solution (HTK), human albumin solution (HAS), or Ringer's solution (RS) and compared with the results obtained immediately after the removal of untreated control samples (C) taken from the same patients. After equilibration in carbogen aerated Krebs-Henseleit solution and precontraction by 3 x 10(-7) M noradrenaline (NE), relaxation induced by 10(-6) M ACh was measured. Only the samples stored in HWB (13.4 +/- 0.4 mN) showed similar maximal contractions with NE to those in the control group (14.4 +/- 0.5 mN), i.e. all those segments which showed both contractions with NE and relaxation with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Transient outward current in human and rat ventricular myocytes.

OBJECTIVE: The aim was to investigate transient outward currents (I(to)) in single myocytes isolated from human heart muscle specimens which were obtained either from patients in terminal heart failure receiving a transplant or from multiorgan donors whose hearts were not suitable for transplantation. METHODS: Using the whole cell patch clamp technique, depolarisation dependent I(to) was investigated in these myocytes, and its electrophysiological characteristics compared to I(to) of rat myocytes. RESULTS: I(to) was observed in ventricular myocytes isolated from failing and non-failing human hearts. The current density of I(to) was similar in cells from failing and non-failing hearts [at +60 mV: 7.9(SEM 1.0) pA.pF-1, n = 9, and 8.7(1.2) pA.pF-1, n = 8, respectively], but smaller in human than in normal rat myocytes, ie, 8.2(0.7) pA.pF-1 (n = 17) v 19.9(2.8) pA.pF-1 (n = 12, six hearts), respectively. Half maximum activation was found at more positive potentials in human than in rat cells, at +21.2(2.0) v +6.4(1.3) mV. In human myocytes, the fraction of non-inactivating outward current at the end of 300 ms long clamp steps was smaller than in rat cells, ie, 22(5%) of peak I(to) in human (n = 17) and 39(5%) in rat cells (n = 12). The potential of half maximum steady state inactivation of rapidly inactivating I(to) in the presence of 0.1 mM Cd2+ was -21.4(0.7) mV in human (n = 15, five hearts), and -35.3(1.0) mV in rat cells (n = 12, six hearts). The late component of outward current showed no potential dependent inactivation in human cells, but underwent steady state inactivation at all potentials positive to -100 mV in rat myocytes. At -100 mV, recovery of I(to) from inactivation took place with a similar time constant, ie, 18(2) ms (n = 7), 24(2) ms (n = 6), and 25(2) ms (n = 4) in cells from three failing and two non-failing human hearts, and from two normal rat hearts, respectively. CONCLUSIONS: In a limited number of cells, I(to) in human ventricular myocytes shows no dramatic differences between cells derived from failing and non-failing hearts. The characteristics of I(to) in human cells were similar though not identical to I(to) in rat heart cells. This current may be a potential target for antiarrhythmic drug action.

Animals↗
PubMed1993

[Effect of dopexamine on the hemodynamics of coronary surgery patients with and without bisoprolol blockade].

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta 1-receptors and direct stimulation of the beta 2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary artery disease classed as NYHA II or III, six without any beta-blocker medication, and six with beta 1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 micrograms/kg/min dopexamine over a period of 15 min and then with 4 micrograms/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗