Systematic evaluation of different approaches for minimizing hemodynamic changes during pneumoperitoneum.

BACKGROUND: Capnoperitoneum (CP) compromises hemodynamic function during laparoscopy. Three therapeutic concepts were evaluated with an aim to minimize the hemodynamic reaction to CP: First, a controlled increase of intrathoracic blood volume (ITBV) by intravenous fluids; second, partially reduced sympathetic activity by the beta1-blocker esmolol; and third, a decrease in mean arterial pressure (MAP) by the vasodilator sodium nitroprusside. METHODS: For this study, 43 pigs were assigned to treatment with fluid and sodium nitroprusside (group A) or with esmolol (group B). In both groups, the pigs were assigned to head-up, head-down, or supine position, resulting in three different subgroups. Invasive hemodynamic monitoring was established including left heart catheter and cardiac oxygen lung water determination (COLD) measurements. Measurements were documented before CP with the animals in supine position, after induction of a 14-mmHg CP with the animals in each body position, after a 10% reduction in MAP by vasodilation, and after an increase in ITBV of about 30% by infusion of 6% hydroxyethylstarch solution. RESULTS: Increasing ITBV improved hemodynamic function in all body positions during CP. Esmolol reduced cardiac output and myocardial contractility. Sodium nitroprusside did not improve hemodynamic function in any body position. CONCLUSIONS: Optimizing volume load is effective for minimizing hemodynamic changes during CP in the head-up and in head-down positions. In general, beta(1)-blockers cannot be recommended because they might additionally compromise myocardial contractility and suppress compensatory reaction of the sympathetic nerve system. Vasodilation has not improved hemodynamic parameters during CP.

Influence of transmyocardial laser revascularization (TMLR) on regional cardiac function and metabolism in an isolated hemoperfused working pig heart.

The mechanism of an indirect revascularization in ischemic myocardium by transmyocardial laser revascularization (TMLR) is not yet fully understood. An improvement of clinical symptoms caused by TMLR is reported in many clinical trials with patients in which a direct revascularization is not possible. An increase of myocardial perfusion through laser channels is doubtful, because the myocardial pressure in the wall is higher than in the cavum. Therefore we measured the local cardiac function (intramyocardial pressure, wall thickness, pressure-length curves) and acute metabolic changes (tissue lactate content, tissue pO2) in ischemic and nonischemic regions before and after TMLR in isolated hemoperfused pig hearts. An isolated heart was chosen because it enabled us to separate coronary flow from flow through ventricular channels. The ischemia was induced by coronary occlusion or microembolization (eight hearts each). It should be noted that microembolization leads to conditions which are more comparable with those found in patients selected for TMLR. In the isolated working heart, the coronary perfusion can be controlled independently from perfusion through the ventricular cavum. Under the ischemic conditions mentioned above, we observed that the intramyocardial pressure in the ischemic region decreased below the left ventricular pressure, so one premise for indirect perfusion was met. TMLR after microembolization led to a significant improvement of regional cardiac work and the tissue oxygen pressure. These acute effects demonstrate the possibility of functional and metabolic amelioration by TMLR after ischemia induced by microembolization in an isolated hemoperfused pig heart.

Isolated hemoperfused heart model of slaughterhouse pigs.

A model of hemoperfused slaughterhouse pighearts is described providing a wide range of applications which leads to a reduction in animal experiments. The size of a pigheart, heart rate, coronary perfusion, metabolism, etc. are more comparable to conditions in patients than those in hearts of small laboratory animals. Global heart function can be assessed either by measuring stroke volume, ejection fraction, Emax etc. in the working model or by measuring intraventricular pressure with balloon catheters in the isovolumetric model. Regional cardiac function can be measured by sonomicrometry and ischemic and non-ischemic areas can be compared. Local metabolic changes are measurable as well with microdialysis. Cardiac function can be kept on any given functional level by infusion of norepinephrine in spite of the fact that functional parameters are lower without adrenergic drive in vitro than in vivo. Stable heart function can be maintained for several hours with only 500 to 1000 ml of blood because the blood is permanently regenerated by a special dialysis system. This model can be applied in many research projects dealing with reperfusion injuries, inotropic, antiarrhythmic or arrhythmogenic effects of certain drugs, immunological rejection, evaluation of imaging systems (NMR, echocardiography etc.) or cardiac assist devices.

Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation.

The study was designed to demonstrate--for the first time in humans--that oxidative stress in the heart indicated by lipid peroxidation is associated with time-dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. >1 y). Significantly increased LPO levels were found (0.27+/-0.04 vs. 0. 13+/-0.02 vs. 0.27+/-0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8+/-3.8 vs. 30.2+/-4.1 vs. 76.7+/-6.5 mU/mg protein), t-SOD (1.57+/-0.10 vs. 1.30+/-0.14 vs. 2.44+/-0.23 U/mg protein) and CuZnSOD (1.09+/-0.08 vs. 0.93+/-0.13 vs. 2.05+/-0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts--despite this adaptation--for complete prevention of myocardial oxidative stress.

[Histologic specimen collection in pulmonary hypertension using percutaneous, transvascular biopsy--animal experiment and initial clinical data]. / Histologische Materialgewinnung bei pulmonaler Hypertonie mittels perkutaner, transvasaler Biopsie (PTB)--tierexperimentelle und erste klinische Daten.

Pulmonary hypertension is a severe multietiological disease largely resistant to treatment. Biopsy is often necessary to establish differential diagnosis. In pulmonary hypertension transbronchial pulmonary biopsy is contraindicated and open lung biopsy is the method of choice. In our paper we report about experimental results in animals and first clinical data on a new biopsy technique (percutaneous transluminal biopsy, PTB) providing access to histology in pulmonary hypertension without the need of surgery. In a subset of animals pulmonary hypertension was produced experimentally. In addition, we carried out the PTB in patients with bronchial carcinoma. Our preliminary results demonstrate that sufficient material could be gained for the histologic evaluation of pulmonary parenchyma and in pulmonary vessels. No complications have been noted so far.

Pituitary adenylate cyclase activating peptides are endothelium-independent dilators of human and porcine coronary arteries.

The PACAPs have been shown to be potent vasodilators in different animal species. Data in humans are still lacking. Therefore we investigated the effects of PACAP 38, PACAP 27 and VIP on isolated human and porcine coronary arteries (HCA and PCA). Our data show, that the PACAPs are endothelium-independent vasorelaxants, which in HCA are slightly more potent than VIP. The N-terminal shortened peptides PACAP 6-38 and PACAP 6-27 also show relatively potent vasorelaxant effects, acting as partial agonists. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, partially reverses the effects of the PACAPs, indicating an involvement of these channels in the mechanism of action.

Effects of prostaglandin E1, prostaglandin E0 and SPM 206 on isolated human coronary arteries.

The effects of PGE1, PGE0 and the stable PGE1-analogue SPM 206 on human epicardial coronary arteries were studied in vitro. The tension of the isolated arterial rings was measured isometrically. After precontraction, concentration-response curves with the compounds were performed. PGE1 and SPM 206 elicited concentration-dependent relaxations which are counteracted by a contractile action in higher concentrations. In PGE0, the contractile action occurred even in lower concentrations. This contraction was antagonized by the selective thromboxane A2 antagonist SQ 29,548, resulting in an equipotent relaxation for all three compounds.

Acute influence of beta-adrenergic antagonists on left ventricular diastolic function: contrasting results after administration of celiprolol and metoprolol.

Various beta-adrenergic receptor antagonists have different effects on myocardial function. A clinical study was performed in 30 patients with symptomatic coronary artery disease and systemic hypertension to compare the effects of single intravenous doses of 0.15 mg/kg celiprolol (n = 16) (third generation beta-blocking agent) and metoprolol (n = 14) (second generation) on left ventricular diastolic function. Parameters derived from pressure, volume, flow, time intervals and their combination were used to characterise diastolic function. After celiprolol administration, parameters of diastolic myocardial function improve (dp/dtip-; relaxation time constant T1, peak filling rate PFR; first-third filling rate FF1/3 or diastolic wall stress-time integral Sigdiasc) or remain unchanged. In contrast, after metoprolol administration parameters of diastolic function seem to be deteriorated (dp/dtip-, T1; Sigdiasc). This indicates an improvement in myocardial relaxation and filling under the influence of celiprolol but not under metoprolol. The left shift of the pressure-volume loops after celiprolol (n = 13), in contrast to metoprolol, supports this interpretation. Celiprolol did not show any deterioration of diastolic function in patients with coronary heart disease and arterial hypertension under these acute conditions.

Diastolic heart function--pathophysiology, characterization, and therapeutic approaches.

In recent years diastolic cardiac function has attracted increasing attention since parameters of diastolic function were found to be altered earlier or more specifically than parameters of systolic function. Diastolic cardiac function is determined by both active (muscular relaxation, redistribution of calcium, synchronization, etc.) and passive (myocardial structure, fibrosis, etc.) factors. As a consequence, a comprehensive assessment of diastolic cardiac function cannot be based on one single parameter. For a complete analysis of diastolic function it is necessary to perform invasive diagnostic procedures involving the measurement of atrial and ventricular pressures, as well as the registration of volume changes with a high time resolution. In addition, it is necessary to measure wall thickness and ventricular configuration, so that apart from filling parameters the stress-strain relationship can be obtained. Noninvasive techniques (Doppler echocardiography, radionuclear ventriculography, apexcardiography) may suggest alterations in diastolic function as well. They ought to be complemented by additional diagnostic procedures (pulmonary pressure, stress testing, etc.). Therapy must consider potentially harmful effects on diastolic function parameters, particularly if changes in myocardial oxygen consumption may result (heart rate, parietal wall stress). Calcium antagonists (verapamil, diltiazem, nifedipine), phosphodiesterase inhibitors (milrinone), beta-adrenergic agonists and antagonists with vasodilating effects (e.g., celiprolol) all have beneficial effects on diastolic myocardial function. A range of diastolic function parameters is being reviewed in the following paper. Their role in the estimation of cardiac function and their responsiveness to therapy in hypertrophy, cardiomyopathy, and coronary heart disease is being discussed.

Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: a double-blind comparison with metoprolol.

Celiprolol is a 'third generation' beta-blocking agent which is claimed to avoid problems associated with simpler beta-blockers, such as vasoconstriction, bronchoconstriction and myocardial depression. A double-blind randomized study was undertaken in 30 patients with coronary artery disease and hypertension to compare the haemodynamic effects of single intravenous doses of 0.15 mg kg-1 celiprolol (N = 16) and metoprolol (N = 14). Following celiprolol administration, the tendency was for myocardial function to improve or remain unchanged; left ventricular end-systolic volume and ejection fraction improved significantly (P less than 0.05). However, following metoprolol administration, the tendency was for myocardial function to deteriorate, with significant falls in cardiac output (P less than 0.05), ejection fraction (P less than 0.05) and velocity of circumferential shortening (P less than 0.01). There was a tendency for peripheral resistance to fall slightly with celiprolol but to rise markedly with metoprolol (pNS). Left ventricular pressure-volume loops showed improved performance with celiprolol and deterioration with metoprolol. Both drugs resulted in increases in coronary flow and myocardial oxygen consumption (P less than 0.05). Metoprolol, but not celiprolol, resulted in some deterioration in regional left ventricular wall motion (P less than 0.05). Celiprolol appears to be haemodynamically advantageous compared to metoprolol in patients with coronary artery disease and hypertension.

[Coronary reserve determination by intracoronary papaverine: effects of various doses on coronary circulation and hemodynamics]. / Bestimmung der Koronarreserve durch intrakoronare Papaverinapplikation: Auswirkungen unterschiedlicher Dosen auf Koronarfluss and Hämodynamik.

In 40 male coronary patients during heart catheterization the coronary flow reserve was investigated by continuous thermodilution in the coronary sinus after intracoronary papaverine application. Simultaneously a number of heart function parameters were recorded. Already the lowest dosage of papaverine (5 mg) was able to induce a maximal flow acceleration. Higher dosages were accompanied with haemodynamic side effects (increase of heart rate and left ventricular end-diastolic pressure, decrease of left ventricular systolic pressure, appearance of myocardial ischemia) without further increase of coronary flow. After at most 5 minutes time the papaverine effects completely disappeared. In conclusion, a safe, short-lasting and repeatable determination of the coronary flow reserve (for instance during PTCA) proved to be possible after intracoronary papaverine injection in low dosages (5 mg).

[Value of diagnostic procedures in heart failure]. / Stellenwert diagnostischer Verfahren bei Herzinsuffizienz.

Strategy for the diagnosis of heart insufficiency is directed to the accomplishment of distinct therapeutic aims. Main factors for diagnostic approaches are pathophysiology and progression of qualitatively and quantitatively different disturbances in cardiac performance. Anamnesis and clinical investigations are irremissible for the evaluation of congestive heart failure. For the detection of noncongestive cardiac insufficiency investigations during exercise are often necessary. Ventriculography ist the standard reference technique for measurement of the systolic and diastolic ventricular functions. For exercise and follow-up investigations non-invasive methods are widely used. Accepted methods are two dimensional and Doppler-echocardiography, quantitative radiocardiography with single-pass bolus technique, and radionuclid-ventriculography. We found a good correlation for the measurement of stroke volume when comparing impedance cardiography with uniplane ventriculography at rest. M-mode echocardiography did not yield sufficiently reliable volumetric data. The new imaging methods, positron emission tomography, magnetic resonance technique, and cine computed tomography are future tools for cardiac output measurements.

[Transfemoral balloon occlusion of the coronary sinus in patients with angina pectoris]. / Die transfemorale Ballonokklusion des Sinus coronarius bei Patienten Angina pectoris.

The aim of the study was to demonstrate the possibility of transfemoral balloon occlusion of the coronary sinus and to detect changes of the left ventricular function during this occlusion in patients with angina pectoris. In 9 of 18 patients a stable occlusion over 15 seconds was performed. There were found only short term negative effects on the left ventricular contraction and relaxation. The coronary sinus pressure increased to 53 +/- 11 mm Hg. Numerous venous anastomoses made it difficult to occlude completely the sinus. The retrograde perfusion of the myocardium reached 20-30% of the antegrade one.

[Determination of pressure-volume relations from ventriculographs using catheter tip manometers]. / Darstellung von Druck-Volumen-Beziehungen aus Ventrikulographien mit Hilfe von Katheter-Tipmanometern.

The evaluation of cardiac function alone from pressure and volume data can lead to misinterpretations. By linking of pressure and volume data a variety of new parameters can be calculated. Computer techniques allow the evaluation not only of cardiac work, but also of acceleration work and the efficiency of heart power. As an example of double blind study with CHD patients the measurement of such parameters under invasive diagnostics is demonstrated, facilitating a detailed evaluation of cardiac function.

[Acute changes of coronary and global hemodynamics in patients with angina pectoris and arterial hypertension caused by celiprolol and metoprolol]. / Akute Veränderungen der koronaren und globalen Hämodynamik bei Patienten mit Angina pectoris und arterieller Hypertonie durch Celiprolol und Metoprolol.

In 30 hypertensives with angina pectoris the acute action of beta-blockers Celiprolol and Metoprolol on the global and coronary haemodynamics was tested within cardiac catheter diagnostics. In accordance with no long-term effects Metoprolol acts negatively inotrope, chronotrope as well as pre- and post-load increasing. Celiprolol lowered the pre- and postload, and increased the cardiac output, but did not influence the heart rate. Both medicaments increased coronary flow and myocardiac oxygen consumption. From the mentioned effects important conclusions for therapy with both Beta-blockers can be derived.