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Biomedical subjects

H R Zerkowski

Publications and source records attributed to H R Zerkowski.

At least 91 records · Page 5Linked to original sources
PubMed1992

Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone.

In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of catecholamines in the human heart.

We studied whether the human heart has spare receptors for beta-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity (pKI values from (-)-[125I]iodocyanopindolol binding) and potency (pD2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of beta-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three beta-adrenoceptor agonists: 50% of maximal response was produced with only 1-3% of beta-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation of beta-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing beta-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1:1 ratio between beta-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for beta-adrenoceptor agonists. This may explain why a decrease in beta-adrenoceptor number leads to a decrease in beta-adrenoceptor function early in the development of heart failure.

Adenylyl Cyclases↗
PubMed1992

Lack of effect of chronic calcium antagonist treatment on beta 1- and beta 2-adrenoceptors in right atria from patients with or without heart failure.

1. We studied the effects of chronic calcium antagonist (calcium entry blocker, CEB; nifedipine, verapamil, diltiazem) treatment on beta-adrenoceptor density (assessed by (-)-[125I]-iodocyanopindolol [ICYP] binding) and subtype distribution in right atria from 65 patients without apparent heart failure undergoing elective coronary artery bypass grafting (CAD-patients) and from 13 patients with moderate heart failure (NYHA class III to class III-IV) undergoing mitral valve replacement (MVD-patients). 2. In CAD-patients atrial beta-adrenoceptor density was 79.3 +/- 7.9 fmol ICYP bound mg-1 protein (n = 18), the beta 1:beta 2-adrenoceptor ratio 69:31%. Chronic CEB-treatment did not affect either atrial beta-adrenoceptor density or beta 1:beta 2-adrenoceptor ratio. 3. In contrast, in CAD-patients chronically treated with beta 1-adrenoceptor antagonists (atenolol, bisoprolol, metoprolol) and CEB, atrial beta-adrenoceptor density was significantly increased (108.6 +/- 10.5 fmol ICYP bound mg-1 protein, n = 21); this increase was due to a selective increase in beta 1-adrenoceptors. 4. In MVD-patients atrial beta-adrenoceptor density (55.5 +/- 8.7 fmol ICYP bound mg-1 protein, n = 7) was significantly lower (P less than 0.05) than in CAD-patients; beta 1:beta 2-adrenoceptor ratio, however, was not changed (67:33%). Chronic CEB-treatment of MVD-patients did not prevent the decrease in atrial beta-adrenoceptors. 5. We conclude that chronic CEB-treatment does not affect human right atrial beta-adrenoceptor density, either in patients without apparent heart failure or in patients with moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Characterization of the beta adrenoceptor subtype(s) mediating the positive inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in isolated human right atrium.

In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced, whereas beta-2 adrenoceptor changes vary depending on the etiology of the disease. Beta Adrenoceptor agonists can be used for short-term inotropic support in chronic heart failure; their clinical efficacy might depend on which beta adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta adrenoceptor subtype(s) involved in the positive inotropic effects of clinically used beta adrenoceptor agonists was characterized on isolated electrically driven human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP 20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI 118,551 (30 nmol/l). Epinine evoked positive inotropic effects through stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2 adrenoceptor component. Both agonists were full agonists causing the same maximum increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax = 0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta-1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full agonist, indicating that part of its positive inotropic effect is indirect via the release of endogenous noradrenaline. Xamoterol did not exert positive inotropic effects, but concentration-dependently slightly decreased basal force of contraction.

Adrenergic beta-Agonists↗
PubMed1992

[Importance of beta 2-adrenergic receptors in heart failure].

Substantial evidence has accumulated that in the human heart both beta 1- and beta 2-adrenoceptors coexist. As a rule, the amount of beta 2-adrenoceptors is higher in the atria (about 30% of the total beta-adrenoceptor population) than in the ventricular myocardium (about 20%). Both beta 1- and beta 2-adrenoceptors couple to adenylate cyclase and mediate positive inotropic effects of isoprenaline and adrenaline on isolated, electrically driven cardiac preparations. In the atria, stimulation of both beta 1- and beta 2-adrenoceptors causes maximal increases in contractile force; in the ventricular myocardium, however, only beta 1-adrenoceptor stimulation maximally increases contractile force, whereas beta 2-adrenoceptor stimulation evokes only submaximal increases. On the other hand, noradrenaline induces its positive inotropic effect on atrial and ventricular preparations solely via beta 1-adrenoceptor stimulation. Because nordadrenaline is the main transmitter of the human sympathetic nervous system, this indicates that under normal physiological conditions, the heart rate and contractility are under the control of cardiac beta 1-adrenoceptors, whereas cardiac beta 2-adrenoceptors play only a minor role, if at all. However, in situations of stress, when large amounts of adrenaline (acting at both beta 1- and beta 2-adrenoceptors with the same affinity) are released from the adrenal medulla, activation of cardiac beta 2-adrenoceptors may contribute to an additional increase in heart rate and/or contractility. In chronic heart failure, cardiac beta-adrenoceptor function decreases (presumably due to endogenous "downregulation" by the elevated catecholamines) and this decrease is related to the severity of the disease (judged clinically by NYHA functional class).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Beta-adrenoceptors in the transplanted human heart: unaltered beta-adrenoceptor density, but increased proportion of beta 2-adrenoceptors with increasing posttransplant time.

To study whether in the (denervated) transplanted human heart beta-adrenoceptors are up-regulated we determined in right ventricular endomyocardial biopsies (weighing 2-7 mg) of 8 heart transplant recipients beta-adrenoceptor density and beta 1:beta 2-adrenoceptor ratio in weekly, later monthly intervals for 6-18 posttransplant months. beta-adrenoceptor density was assessed by 1-2 concentration (-)-[125I]-iodocyanopindolol (ICYP, 200 and 150 pmol/l) binding, the beta 1:beta 2-adrenoceptor ratio by a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712 A (500 nmol/l). In biopsies taken from the donor hearts immediately before transplantation beta-adrenoceptor density was 64.5 +/- 6.3 fmol ICYP bound/mg protein (n = 5), the beta 1:beta 2-adrenoceptor ratio 81.2 +/- 2.2:18.8 +/- 2.2%. beta-Adrenoceptor density did not change during the whole period investigated; it was in the first 9 posttransplant weeks 73.1 +/- 8.3 (n = 22) and after 4-18 months 74.2 +/- 7.6 fmol/mg protein (n = 16). In contrast, with increasing posttransplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20% (n = 17), after 16 weeks 75:25% (n = 10) and after 25-80 weeks 65:35% (n = 7). We conclude that in the first 18 posttransplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decline in beta 1- and increase in beta 2-adrenoceptors with increasing posttransplant time. As noradrenaline acts in the human heart solely at beta 1-adrenoceptors, while adrenaline activates both beta 1- and beta 2-adrenoceptors with about the same potency, with increasing posttransplant time (and increasing proportion of beta 2-adrenoceptors) adrenaline may play an important role for regulation of contractility and/or heart rate in heart transplant recipients.

Adolescent↗
PubMed1991

[The concept of lung and heart-lung preservation within the scope of multiple organ procurement].

Preservation of the lung is still one of the most challenging problems, because due to limited procurement time not all organs available can be used. The most common procurement technique is flush perfusion of the pulmonary artery system. Alternative methods in clinical use are either the autologous working heart-lung preparation or donor core-cooling (DCC). The own concept presented here, modified to the special demands of multi-organ-procurement, combines DCC and interstitial equilibration adapted to intracellular ion concentration. DCC is induced by extracorporeal circulation (ECC) using a transportable heart lung machine including a highly effective cooling system: cooling circuit based on two parallel heat exchangers with ice-water cooling produced by a high-pressure overflow of a low-temperature ice block (-40 degrees C). While cooling by ECC stepwise hemodilution is achieved by priming volume and incorporation of the cardioplegic solution (Bretschneider-HTK). The aim of equilibration is to lower the extracellular levels of sodium and calcium, and to increase the level of potassium. Additionally, the buffer capacity of donor blood is increased by the incorporated histidine-buffer system (alpha-stat). To avoid donor organ edema the time of ECC should be as short as possible. Using our system donor organ temperatures below 10 degrees C are reached within less than 30 min. In addition to ECC, lung surface cooling is achieved by external overflow with cold arterial blood (internal mammary artery). Besides lung preservation the main advantage of this concept is the profound precooling of all visceral organs before their individual flush perfusion.

Animals↗
PubMed1991

Development of beta-adrenoceptor number and subtype distribution in the transplanted human heart.

The transplanted human heart is a denervated organ and thus may exhibit beta-adrenoceptor supersensitivity. To monitor possible beta-adrenoceptor changes in the transplanted human heart we assessed, in right ventricular endomyocardial biopsies from eight heart transplant recipients, beta-adrenoceptor number (by (-)-[125I]-iodocyanopindolol [ICYP] binding) and beta 1:beta 2-adrenoceptor ratio (by inhibition of ICYP binding with a beta 1-adrenoceptor saturating concentration of CGP 20712 A, 500 nM) in weekly, later monthly, intervals for 6-18 post-transplant months. In the biopsies of the transplanted hearts, beta-adrenoceptor number was significantly higher than in the right ventricular membranes of the explanted native hearts of the patients; during the whole period, the biopsies' beta-adrenoceptor number was quite stable and no significant increase or decrease was observed. In contrast, with increasing post-transplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20%, while after 4-18 months it had decreased to 66:34%. We conclude that in the first 18 post-transplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decrease in beta 1- and increase in beta 2-adrenoceptors with increasing post-transplant time. This may have important pathophysiological consequences for regulation of contractility and/or heart rate by endogenous catecholamines in heart transplant recipients.

Adolescent↗
PubMed1991

[Interdisciplinary management of perforating heart injuries].

Penetrating cardiac injuries are being observed in urban regions with increasing frequency; due to improved advanced trauma life support ascending numbers of trauma victims are reaching the trauma centers still alive. The main pathophysiological determinant is acute pericardial tamponade. The time course of the patients' circulatory state cannot be predicted due to the nonlinear course of the pressure-volume relationship. Thus only after clinical diagnosis is made and if the circulation is poor should on-the-spot emergency subxiphoidal pericardiocentensis be considered and endotracheal intubation is indicated restrictively. The concept of clinical emergency room management is as follows: (1) Under stable circulatory conditions urgent exploratory pericardiotomy should be performed following sonographic confirmation; (2) in compensated state of shock and with clinical signs of tamponade immediate pericardiotomy should be done simultaneously with induction of anesthesia, abstaining from any diagnostic procedures; (3) in life-treating situations or under resuscitation emergency sternotomy should be performed by the surgeon present, aiming to control bleeding. Reconstruction can be done in cooperation with the cardiothoracic surgeon. The operative techniques used may extend from simple suturing of the myocardial injury to emergency aortocoronary bypass grafting. By quick interdisciplinary emergency management including basic cardiac surgical techniques (performed ideally by the trained general or trauma surgeon) even penetrating cardiac injuries can be treated with acceptable prognosis.

Cardiac Tamponade↗
PubMed1991

[Therapeutic concepts in treatment of circulatory and heart failure in surgery].

Perioperative circulatory disorders in patients may take the form of a transitory reduction in oxygen transport to the peripheral tissues (pre-shock), manifest circulatory insufficiency in the presence or absence of concomitant heart insufficiency or general congestive heart failure due to the destabilization of an preexisting heart disease. The least problematical stage in this programme of therapy is the treatment of transitory perioperative circulatory insufficiency by manipulation of the oxygen transport system using the following means: comparative volume optimization [according to the central venous pressure (CVP)], positive inotropic support with dobutamine (5-10 micrograms.kg-1.min-1), monitoring of the blood pressure, heart rate and oxygen consumption and, in severe cases, insertion of a Swan-Ganz catheter. In manifest circulatory insufficiency, sepsis or acute congestive heart failure, the Swan-Ganz catheter seems to be obligatory. In such cases, the positive inotropic therapy is based on catecholamines of medium (dobutamine) or high (epinephrine) positive inotropic efficacy, as a normal pattern and functioning of beta-adrenoceptors can be assumed in such cases if there is no history of cardiac insufficiency. The systemic vascular resistance (SVR) is adjusted to 800-1200 n.s.cm-5 to relieve the working capacity of the heart and to maintain sufficient perfusion pressure by means of constrictors (phenylephrine, norepinephrine) or dilators [nifedipine, nitroglycerin or, if necessary, angiotensin-converting-enzyme (ACE) inhibitors].(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1990

Differential regulation of human cardiac beta-adrenergic and muscarinic receptors by chronic beta-adrenoceptor antagonist treatment.

In patients undergoing coronary artery bypass grafting chronic beta 1-adrenoceptor antagonist treatment increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number and decreased muscarinic M2-receptor number. Concomitantly, the M2-receptor-mediated negative inotropic effect of carbachol was reduced, while the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was not altered. The beta 2- adrenoceptor mediated positive inotropic effect of procaterol, however, was markedly enhanced. We conclude that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number, sensitizes beta 2-adrenoceptor function and desensitizes M2-receptor function in the human heart.

Adrenergic beta-Antagonists↗
PubMed1990

Chronic beta 1-adrenoceptor antagonist treatment sensitizes beta 2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium.

1. In 64 patients undergoing coronary artery bypass grafting the effects of chronic beta 1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial beta-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated. 2. The beta 1-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3. Concomitantly, activation of right atrial adenylate cyclase by 10 microM GTP, 10 microM isoprenaline and 1 microM forskolin was enhanced and inhibition by 100 microM carbachol was diminished. 4. On isolated, electrically driven right atria the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was - even with beta 1-adrenoceptor number increased - not altered, while the beta 2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased. 5. It is concluded that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number and concomitantly sensitizes beta 2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.

Adenylyl Cyclase Inhibitors↗
PubMed1990

[Diagnosis and therapy of acute traumatic aortic rupture].

Aortic transection is defined as complete or partial dehiscence of the aortic wall layers. Aortic transections are seen in 16% of all lethal traffic accidents. The quality of the first emergency care outside hospital and the organization of rescue systems result in an increasing number of patients (espec. with life-threatening multiple injuries incl. atypical aortic lesions) reaching a trauma-center. Guide-lines for surgical indications are: 1. emergency-operation in case of symptomatic transection incl. simultaneous surgery of concommitant lesions. 2. Urgent operation following primary hemodynamic stabilisation in cases of isolated or asymptomatic transection. 3. In cases of concommitant lesions with surgical priority, delayed operation of asymptomatic transection. The perioperative letality claims up to 20%. Next of operative complication paraplegia remains the most deleterious problem. Despite different methods of protection on the spinal cord the incidence of paraplegia persists in the range of 5-10%.

Aorta, Thoracic↗
PubMed1989

Subtype-selective up-regulation of human saphenous vein beta 2-adrenoceptors by chronic beta-adrenoceptor antagonist treatment.

To study beta-adrenoceptor antagonist-induced changes in human vascular beta-adrenoceptors, we determined the effects of chronic treatment with different beta-adrenoceptor antagonists without intrinsic sympathomimetic activity (ISA) on beta 2-adrenoceptor density (assessed by (-)-[125I]-iodopindolol binding) in human saphenous vein membranes obtained from patients undergoing coronary artery bypass grafting. In patients chronically treated with the non-selective beta-adrenoceptor antagonists propranolol or sotalol, the density of saphenous vein beta 2-adrenoceptors was significantly higher than in control (i.e. patients not treated with beta-adrenoceptor antagonists), whereas in patients chronically treated with the selective beta 1-adrenoceptor antagonists metoprolol or bisoprolol it was not different from control. It is concluded that beta-adrenoceptor antagonists without ISA increase human saphenous vein beta 2-adrenoceptors in a subtype-selective fashion.

Adrenergic beta-Antagonists↗
PubMed1989

Do human cardiac beta-2 adrenoceptors play a (patho)physiological role in regulation of heart rate and/or contractility?

There can be no doubt that in human heart in addition to beta 1-adrenoceptors, functional beta 2-adrenoceptors exist. Their (patho)physiological role in regulating heart rate and/or contractility, however, is still an open question. Under normal physiological conditions cardiac beta 2-adrenoceptors may not be of functional importance, since heart rate and contractility seem to be under the control of noradrenaline that in the human heart acts nearly exclusively at beta 1-adrenoceptors. However, in situations of stress when large amounts of adrenaline are released from the adrenal medulla additional stimulation of cardiac beta 2-adrenoceptors may contribute to increases in heart rate and/or contractility. Moreover, in endstage congestive cardiomyopathy where cardiac beta 1-adrenoceptors are selectively down-regulated, cardiac beta 2-adrenoceptors may substitute for the loss of beta 1-adrenoceptors to maintain (at least partially) contractility; under these conditions beta 2-adrenoceptor agonists, like dopexamine, may be of beneficial therapeutic effect. While a decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure, it is not always due to a selective reduction in cardiac beta 1-adrenoceptors: in mitral valve disease both cardiac beta 1- and beta 2-adrenoceptors decline concomitantly in relation to the degree of heart failure. It is, therefore, doubtful whether under these conditions beta 2-adrenoceptor agonists may also be useful to support the failing heart.

Dopamine↗