C1-INH and its effect on infarct size and ventricular function in an acute pig model of infarction, cardiopulmonary bypass, and reperfusion.

BACKGROUND: Recent studies suggest that complement inhibition reduces reperfusion injury. A clinical setting with local application of a C1 esterase inhibitor (C1-INH) has been modeled in an animal study in order to further investigate these findings. METHODS: In 21 pigs, the left anterior descending coronary artery (LAD) was occluded distally to the first diagonal branch for 2 hours (h), including 1 h of cardioplegic arrest during CPB. After release of the coronary snare, C1-INH or NaCl (control) was applied to the aortic root. Thereafter, the aortic cross-clamp was removed and the heart was reperfused for 30 minutes before weaning from CPB. Left ventricular pressure volume analysis was performed by a multielectrode conductance catheter and the area at risk and infarct size were determined from excised hearts. RESULTS: The following data were observed (mean+/-SEM) for the control group and the C1-INH group, respectively, after 1-h ligation of the LAD: heart rate (HR) 86+/-3 and 93+/-6 beats/min, stroke volume (SV) 1.2+/-0.1 and 1.2+/-0.1 ml/kg, aortic pressure (AoP) 83+/-6 and 87+/-5 mmHg, left ventricular end-diastolic pressure (LVedP) 12+/-1 and 11+/-2 mmHg; two hours after weaning from CPB: HR 106+/-9 and 123+/-4 beats/min, SV 0.9+/-0.1 and 0.9+/-0.1 ml/kg, AoP 65+/-5 and 79+/-7 mmHg, LVedP 9+/-1 and 8+/-1 mmHg. Conductance catheter measurements showed no improved left ventricular performance after C1-INH application. Infarct size to area at risk ratio was 61.5+/-4.2% for controls and 61.4+/-4.8% for C1-INH. CONCLUSIONS: Intracoronary application of complement inhibitor in an acute infarction model, which mimicked a clinical setting of urgent coronary bypass grafting after ischemia, has been shown to neither influence the area of infarction, nor the ventricular function.

Diastolic unloading and improved LV pump efficiency early after repair of the insufficient mitral valve.

BACKGROUND: This study aimed to evaluate the acute effect of mitral valve repair (MVR) on LV hemodynamics and geometry in patients with normal ventricular function. METHODS: In 10 patients with severe mitral regurgitation undergoing MVR, pressure-volume relationships were recorded before annuloplasty prior to and after hemodilution and after MVR during stable circulatory condition, using the conductance catheter technique (CC). Analyses were done off-line; volume calibration was based on data obtained after completion of valve repair (mean +/- s.d.). RESULTS: CC showed that only 61 +/- 15 % of left ventricular output was ejected into the systemic circulation, regurgitation volume being 39 +/- 15 %. MVR led to a reduction in LV stroke work index from 4.7 +/- 1.8 mm Hg x l x m (-2) at before valve repair to 2.2 +/- 1.0 mm Hg x l x m (-2) after surgery at unchanged cardiac index. LV diastolic filling parameters improved: LV relaxation time constant tau decreased from 52 +/- 15 to 37 +/- 11 ms and dP/dt (min) increased from - 873 +/- 231 to - 1286 +/- 283 mm Hg x s (-1). CONCLUSIONS: Despite cardioplegic arrest, MVR leads to acute improvement of diastolic LV function early after the operation. This may explain why valve repair has an acute positive effect in patients with impaired LV function.

Effect of cardiopulmonary bypass and hemofiltration on plasma cytokines and protein leakage in pigs.

BACKGROUND: The hypothesis that an inflammatory process during and after cardiopulmonary bypass (CPB) impairs hemodynamics and causes increased capillary protein leakage and that this is possibly ameliorated by hemofiltration (HF) was tested. METHOD: 26 anesthetized pigs were subjected to 120 min CPB (90 min cardioplegia followed by 30 min reperfusion, combined with conventional and modified HF in 13 animals). Hemodynamics, leukocytes, cytokines (IL-1ra, IL-8, IL-10, TNF-alpha), LNPI, plasma protein, and the half-life of i.v. injected Evans Blue (t/2) were assessed before and after CPB. RESULTS: CPB was followed by depression of left ventricular function and activation of inflammatory mediators. Although a slight elimination of some inflammatory mediators occurred, HF did neither improve cardiac function nor reduce the inflammatory process. Plasma protein was lost during CPB and hemofiltration by protein trapping to the surfaces of the CPB system, by filtration across the hemofilter, and by increased microvascular filtration (solvent drag). The latter was probably due to an increased filtration pressure in consequence of the reduction of plasma colloid osmotic pressure by the crystalloid primed CPB. t/2 did not indicate an increased microvascular protein leakage after CPB. CONCLUSION: Hemofiltration is ineffective in improving cardiac function or reducing the inflammatory response of CPB in the pig model.

Pulmonary function after biventricular bypass for autologous lung oxygenation.

OBJECTIVE: Biventricular bypass (BVB) with autologous lung perfusion is an attractive concept to ameliorate systemic inflammatory response by eliminating the oxygenator from the extracorporeal circulation. The effect of biventricular bypass as compared to heart-lung bypass (HLB) on pulmonary function parameters was therefore studied in an experimental model. METHODS: Heart-lung bypass using a membrane oxygenator or biventricular bypass using the autologous lung for gas exchange was performed for 120 min in an alternating series of 12 mongrel dogs with the heart arrested for 90 min by crystalloid cardioplegia and 30 min reperfusion, followed by a 120 min observation period. Systemic (CO, SVR) and pulmonary hemodynamics (PVR), extravascular lung water (EVLW, double indicator), gas exchange (FiO(2), PaO(2), PaCO(2)), lung compliance (PC), and ventilation (RMV) at FiO(2)=0.5 required to maintain PaCO(2) at 40 mmHg, were measured. Blood cell counts (Leuco, Thrombo) were performed. RESULTS: All animals were weaned from extracorporeal circulation without inotropes, no differences were observed in cardiac output and blood pressures. The following data were obtained in % change from pre-bypass values 60 min after extracorporeal circulation (*:P<0.05, HLB vs. BVB): PVR, +108 vs. +45*; EVLW, +21 vs. -2*; PC, -12 vs. +4*; PaO(2), -8 vs. +21; RMV, +21 vs. +2*; Leuco, -65 vs. -12*; Thrombo, -62 vs. -35*. CONCLUSION: During and after heart-lung bypass the lung is subject to severe ischemia-reperfusion injury as indicated by edema, cell trapping, and impaired gas exchange. The data demonstrate superior preservation of pulmonary mechanics and function after biventricular bypass as compared to heart-lung bypass and support the clinical strategy of using biventricular bypass in patients with impaired lung function.

Effect on coronary artery flow reserve and resistance in the remote area after acute coronary artery occlusion in the pig model.

BACKGROUND: It has been reported that vasodilator function in remote myocardial regions supplied by "angiographically normal" coronary arteries is impaired in patients after acute myocardial infarction (MI). The aim of this study was to determine whether coronary artery flow reserve and coronary artery resistance in remote, nonischemic areas are also altered in experimental MI. METHODS: Experiments were performed in anesthetized pigs. In group 1 infarction was induced by ligation of the left-anterior descending artery (LAD); group 2 consisted of sham-operated animals. Hemodynamic parameters, coronary artery resistance, and myocardial blood flow (MBF) were measured before and 4 hours after MI under rest and during infusion of adenosine. RESULTS: Coronary artery dilation by adenosine caused a similar increase in MBF before and 4 hours after coronary artery occlusion. Resting MBF after acute MI was not altered, although a significant reduction (15%; P < .04) in mean aortic pressure was observed compared with baseline. Coronary artery resistance was significantly reduced by adenosine (P < .04) before MI, as well as at 4 hours after MI (P < .03). Coronary artery flow reserve was not adversely affected. The sham-operated animals showed similar results without any significant differences between the two study groups. CONCLUSION: This study indicates that an acute MI in pigs did not increase coronary artery resistance in the remote area after MI and therefore did not adversely affect coronary artery flow reserve in the nonischemic vascular bed. Further studies are necessary to fully understand the exact mechanism of the alterations in remote flow reserve of patients after MI.

Spectrotemporal mapping of high-resolution ECGs in experimental myocardial infarction: comparison with time-domain analysis and epicardial electrograms.

The study was undertaken to evaluate the relationship of signal-averaged ECG (SA-ECG) readings in the frequency domain (STM) and epicardial electrograms (EE) recorded before and after acute myocardial infarction (AMI) in pigs and to compare the changes with findings in time-domain analysis (TDA). In 20 pigs the left anterior descending artery (LAD) was ligated. Prior to ligation, a SA-ECG was recorded (method of Simson) and bipolar electrodes were used to register EE in the areas supplied by the LAD and the circumflex artery (CIRC). Five minutes after LAD ligation, all measurements were repeated. Time-domain parameters were QRS duration (QRS D) and the duration of the signal below 30 microV (LAS 30). Beginning at a point of 20 ms before the QRS end, the frequency spectra (0-200 Hz) of 25 segments of 80-ms duration at the QRS end were analyzed. The volumes below the 25 curves were analyzed separately for 0-50 Hz, 51-100 Hz, 101-150 Hz, and 151-200 Hz. After AMI, five pigs died within 7 minutes. In 15 pigs, QRS D as well as LAS 30 lengthened significantly (P<0.05; P<0.001). Spectrotemporal mapping (STM) showed a significant decrease of the frequencies above 50 Hz (51-200 Hz) in the entire group and in the animals with late potentials (P<0.05). EE of the LAD area were significantly prolonged (P<0.01); this did not correlate with the changes in STM parameters. In pigs acute myocardial infarction causes a shift towards lower frequencies in the STM which most likely reflects the slowed depolarisation in the ischemic area.

Effect of dopamine and atrial pacing on stunned myocardium.

OBJECTIVE: Post-ischaemic stunned myocardium shows an impaired function at restored coronary blood flow, but performance can be normalized by positive inotropic stimulation. The power of stunned myocardium, however, is not augmented with increasing heart rate by atrial pacing, which is in contrast to intact areas. This pathological response is mitigated by inhibiting the degradation of cyclic AMP. The present experiments studied the effect of stimulating cyclic AMP formation by dopamine on the response of stunned myocardium to atrial pacing. METHODS: In anaesthetized (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused for 2 h. Subsequently, heart rate was raised by right atrial pacing before and during intravenous infusion of dopamine (10 microg/kg per min). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from 11 experiments are presented. RESULTS: After 2 h LAD reperfusion, LAD blood flow and power were 100% and 36% of pre-ischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed significantly (111% of control). Increasing heart rate by +36 and +70 from 94 beats/min increased the power of the intact area to 161% and 183% of control; the power of the stunned myocardium decreased to 34% and 19% of pre-stunning control. Dopamine increased the power of the stunned region to 143% of the pre-stunning level and the power of the intact area to 206% of control. Increasing heart rate by +34 and +70 from 113 beats/min during dopamine, increased the power of the intact myocardium to 288% and 344% of control and the power of the stunned region to 177% and 174% of the pre-stunning level. CONCLUSIONS: The data confirm the pathological response of stunned myocardium to atrial pacing and the recruitment of a functional reserve by catecholamines. The adverse effect of pacing on the function of stunned myocardium is abolished by positive inotropic stimulation. Possibly, the cyclic AMP system is involved in the normal response to pacing and this pathway is disturbed in stunned myocardium; other defects are not excluded or supported, however. Physiologically increased heart rate by an increased activity of the sympathetic nervous system, is probably not accompanied by a reduced power of stunned myocardium, due to the associated positive inotropic stimulation.

Effect of milrinone and atrial pacing on stunned myocardium.

OBJECTIVE: Most mammalian cardiac muscles show a positive force-frequency relation, which is turned into a negative relation in failing hearts. Stunned myocardium shows similar defects as failing myocardium, it has a functional reserve recruitable by positive inotropic interventions, and possibly shows a disturbed response to increased heart rate. The present experiments compare in vivo the response of stunned and intact myocardium to atrial pacing before and during inotropic stimulation by milrinone. METHODS: In anaesthetised (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused. Heart rate was raised by right atrial pacing after 90 min reperfusion before and during i.v. milrinone (105 microg/kg bolus + 8 microg/kg per min infusion). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from ten experiments are presented. RESULTS: After 90 min LAD reperfusion, LAD blood flow and power were 110 and 36% of preischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed (102% of control). Pacing from 87 to 164 per min increased the power of the intact area (+96%), the power of the stunned myocardium decreased (-64%). Milrinone increased the power of the stunned region to 72% of the pre-stunning level and the power of the intact area by +51%. Pacing from 111 to 164 per min during milrinone increased the power of the intact myocardium to the same level as before milrinone, the power of the stunned region did not change. CONCLUSIONS: Stunned myocardium responds pathologically to atrial pacing with a negative staircase in contrast to the positive staircase of intact myocardium. Inotropic stimulation by the phosphodiesterase inhibitor milrinone recruited the functional reserve of stunned myocardium. Milrinone did not restore a positive staircase in stunned myocardium, but power was maintained during atrial pacing. The pathological staircase of stunned myocardium may arise from an impaired availability of cyclic AMP, but the data do not exclude defects in calcium handling, a dysfunction of the sarcoplasmic reticulum, or an impaired Ca-sensitivity of the myofilaments.

[Experimental principles for preserving annulo-ventricular integrity of the mitral valve]. / Experimentelle Grundlagen zur Erhaltung der anuloventrikulären Integrität der Mitralklappe.

Despite numerous improvement in cardiac surgery the results in mitral valve replacement are still not satisfactory, since impaired left ventricular function continues to be a problem during the postoperative course. In order to investigate the effect of mitral valve replacement on left ventricular function canine experiments were performed: During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the ventriculo-annular continuity. Flexible wires were slung around the chordae of the subvalvular mitral apparatus and brought to the outside through the left ventricular wall. Left ventricular diameters were measured by sonomicrometry, left ventricular stroke volume, left ventricular enddiastolic volume and ejection fraction by dye dilution technique as well as left ventricular and aortic pressure by catheter tip manometers. After finishing cardiopulmonary bypass control values were registered and different preload values achieved by volume loading with blood transfusions to left ventricular enddiastolic pressures of 12 mm Hg. Subsequently under normovolumic conditions the chordae tendineae of the anterior and posterior papillary muscles of the mitral valve were cut from the outside, while the heart was beating, by application of electrocautery on the steel wires. Following severance of the ventriculo-annular continuity of the mitral valve again function curves of left ventricular hemodynamics were made during volume transfusions. When the chordae had been divided the left ventricular enddiastolic diameter increased by 10% in the major axis, while in the minor axis no significant changes occurred. The systolic shortening was impaired substantially by reduction of 43% during the ejection phase when the subvalvular mitral apparatus had been severed. Left ventricular enddiastolic volume was increased by 18% at any preload level, while left ventricular ejection fraction was reduced by 16%. Consequently left ventricular stroke volume was decreased by 24% at any left ventricular enddiastolic volume, when the chordae had been divided. It can be concluded that left ventricular geometry is changed when the annulo-ventricular continuity has been interrupted at mitral valve replacement: The major axis of the left ventricle is increased and the enddiastolic volume is augmented. The left ventricle is only able to eject the same stroke volume at higher preload levels when the chordae tendineae have been divided. The same cardiac performance can only be achieved by volume loading and at the expense of higher wall tension, which leads to unfavorable conditions in terms of cardiac muscle mechanics with reduced exercise tolerance. These data speak for preservation of the annulo-ventricular continuity in mitral valve replacement. Provided that these results from acute canine experiments can be transferred to humans, one would suggest that preservation of the mitral subvalvular apparatus is of importance in patients with dilated hearts and with impaired left ventricular function.

Bi-ventricular function assessed intraoperatively before and after anatomical correction of transposition of the great arteries.

After anatomical correction of transposition of the great arteries (TGA), the left ventricle (LV) is forced to develop systemic pressures without having had time for adaptation. Thus, one might expect dilatation of the LV at least in the very early intraoperative period following the operation. In nine patients with TGA aged 8-24 days (median 9.5 days) which were selected for arterial switch operation (ASO), Dacron-patch mounted thin piezoceramic transducers were attached intraoperatively by fibrin glue to opposite epicardial surfaces of the right (RV) and/or LV for continuous assessment of external minor diameters (RVD, LVD; sonomicrometry) before and after correction. Right and left ventricular pressures (RVP, LVP) were measured simultaneously and pressure-diameter loops were generated. Right and left ventricular power indices (RVPi, LVPi: = HRxVPxVsD) was calculated from heart rate, ventricular pressures, and systolic shortening of the respective ventricular diameter (RVsD, LVsD). Data obtained during circulatory steady-state immediately before extra-corporeal circulation (ECC) and up to 45 min after ECC were compared. By avoiding volume overload (CVP < or = 10 mmHg) at weaning off ECC and by lowering the systemic vascular resistance and, thus, LV afterload (approximately 8 micrograms.kg-1 min-1 dobutamine), the LV developed systemic pressure (70 +/- 7 vs. 41 +/- 4 mmHg) at unchanged diastolic LV end-diastolic pressure (LVedP) (10 +/- 3 mmHg). Left ventricular power index increased by 45 +/- 25%, although the extent of systolic shortening of LVD was reduced by 20 +/- 10%. Simultaneously, the RV was effectively unloaded (RVedP: 8 +/- 3 vs 11 +/- 6 mmHg; RVP: 39 +/- 7 vs 53 +/- 9 mmHg; RVPi: -42 +/- 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Reservoir characteristics of Mainz pouch studied in animal model. Osmolality of filling solution and effect of oxybutynin.

In a canine model of the Mainz pouch, intracavitary pressure and compliance were measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water) solutions of saline. Wall properties of small- and large-bowel segments of the pouch were assessed individually by sonomicrometry. Intraluminal pressures increased more steeply during filling with hyperosmotic solution, resulting in reduced distensibility of small- and large-bowel segments. Additionally, instillation of the hyperosmotic solution resulted in increased amplitudes and frequency of intracavitary pressure waves. The results indicate that this was the result of a combination of intensified bowel contractions and an increased mural tension. Topical application of oxybutynin abolished these effects. These findings are reviewed in light of the nocturnal increase in urine osmolality, its correlation with nocturnal incontinence in patients with enterocystoplasty, and possible treatment choices.

Importance of the left ventricular subvalvular apparatus for cardiac performance.

The importance of the subvalvular mitral apparatus for left ventricular performance was studied in eight anesthetized dogs. During extracorporeal circulation St. Jude Medical mitral valve prostheses were implanted preserving the chordae tendineae. Flexible wires were slung around the chordae tendineae and brought to the outside through the left ventricular wall to cut the chordae tendineae by electrocautery in the closed beating heart. The left ventricular diameters were measured by sonomicrometry, left ventricular stroke volume and enddiastolic volume by dye dilution, and left ventricular pressure by catheter tip manometer. Data were collected at different preloads achieved by volume loading with blood before and after the chordae tendineae were cut. The results showed that after the chordae tendineae had been cut left ventricular systolic pressure, heart rate, diastolic and systolic diameters of the left ventricle along the minor axis were not different from the pre-cut values at any left ventricular enddiastolic pressure. However, significant differences were observed for maximum dp/dt (-15%), major axis diastolic diameter (+10%) and systolic shortening (-40%), enddiastolic volume (+18%) at any left ventricular enddiastolic pressure, and stroke volume (-24%) at any enddiastolic volume level. The data demonstrate that the subvalvular apparatus not only maintains physiologic valve function, but contributes significantly to left ventricular performance. The impairment of left ventricular function following removal of the subvalvular apparatus might be aggravated in pre-injured hearts in mitral valve disease. Consequently, the subvalvular apparatus should be preserved in mitral valve replacement whenever possible.

Importance of the mitral apparatus for left ventricular function: an experimental approach.

In an experimental study of 31 anesthetized dogs the importance of the mitral apparatus for the left ventricular function was investigated. During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the mitral subvalvular apparatus. Flexible wires were slung around the chordae tendineae and exteriorized through the left ventricular wall to cut the chordae by electrocautery from the outside when the heart was beating again. External and internal left ventricular dimensions were measured by sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters around the ascending aorta, left ventricular end-diastolic volume by dye dilution technique, and left ventricular pressure by catheter tip manometers. Different preload levels were achieved by volume loading with blood transfusion before and after cutting the chordae tendineae. When the chordae had been divided peak systolic left ventricular pressure did not change. Heart rate only increased at the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained unchanged at higher preload levels. Cardiac output decreased significantly up to -9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload level. Significant reductions were also seen in systolic shortening in the left ventricular major axis (by external measurements -27%, by internal recording -43%). Left ventricular end-diastolic dimensions increased in the major axis by +2% when recorded externally, by +10% when measured internally. Systolic and diastolic changes in the minor axis were not consistent and different in the external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the serotonin-antagonist ketanserin on the function of ischaemic and normally perfused myocardium and modification by beta-1-blockade in anaesthetized normotensive dogs.

The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute hypertension in coronary bypass surgery. The present study was performed to investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of myocardium supplied by the left descending coronary artery (LAD) and the left circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia to decrease sdLLAD (-48%) was achieved by LAD stenosis (QLAD -47%). Concomitantly, edLLAD increased by 8%. However, the other variables did not change. Then KAS was given i.v. (0.15 + 0.15 + 0.30 + 0.6 mg/kg) at 15-min intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables were not affected. This functional recovery of ischaemic myocardium was attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis. The ischaemic area was not irreversibly damaged, however, as proven by the recovery of prestenotic sdLLAD values after release of the stenosis. The improved systolic shortening of ischaemic myocardium following KAS did not result from restored QLAD due to post-stenotic vasodilation or break up of platelet aggregates (QLAD did not increase) or from reduced afterload (AoP did not decrease). Obviously, it was mediated by beta-1-receptors, as shown by the attenuation of the beneficial effect of KAS by pretreatment with MET.

Cyclic motion of ischemic ventricular wall area and hydrodynamics of the blood during ejection.

Analysis of dimensional changes of ischemic left ventricular wall segments evidenced a dilation immediately after onset of ejection; thereafter, contraction appears delayed but almost regular. This biphasic systolic wall motion was correlated in a retrospective study to parameters indicating local intramural disorders, intraventricular load changes, and hydrodynamics of the blood during ejection. Hemodynamic data stored on a 16-track tape recorder were analyzed from 12 consecutive experiments in anesthetized dogs in which the left circumflex coronary artery (LCX) was gradually narrowed (coronary flow restriction greater than or equal to 50%). Left ventricular and aortic pressure, aortic blood velocity (v), acceleration/deceleration (dv/dt), and instantaneous stroke volume (m = integral of v*dt), and segment lengths of normal and ischemic myocardial regions (sonomicrometry) were numerically evaluated with 5 msec resolution. Systolic shortening of the intact myocardium correlates with the diminution of the intraventricular volume during ejection (r greater than 0.98). In contrast, ischemic segments dilate early during systole when the blood is accelerated; the extent of dilation depends on the degree of coronary flow reduction. The time course of lengthening coincides with the development of force F = m*dv/dt (r greater than 0.90) originating from regularly contracting parts of the ventricle. During blood deceleration, ischemic wall segments shorten as F turns to negative (r greater than 0.95). Thus, the wall motion of ischemic myocardial regions is modulated by the hydrodynamic force resulting from acceleration and deceleration of blood consecutively impeding and supporting the systolic function of the ischemic myocardium in the course of ejection.

Effect of the 'specific bradycardic agent' alinidine on the function of ischemic myocardium.

In patients with coronary artery disease, the reduction of heart rate (HR) by beta-blockers can further impair myocardial function by reducing the contractility and coronary perfusion. This is possibly not the case for "specific bradycardic agents" like alinidine (ALI). The effect of ALI on ischemic myocardium, therefore, was studied in anesthetized open-chest dogs measuring left ventricular end-diastolic pressure (LVedP), dP/dt, aortic pressure (AoP) by catheter tip manometers, coronary blood flow (Q) electromagnetically, end-diastolic length (edL) and systolic shortening (sdL in %edL) of ischemic (RISC) and non-ischemic (NISC) wall segments by sonomicrometry. Group A (n = 11): Left coronary artery constriction to reduce Q (-53%) and poststenotic sdL (-54%), then i.v. injection of ALI (0.25 + 0.25 + 0.5 + 1.0 mg/kg), thereafter atrial pacing at HR before ALI. Group B (n = 9): Installation of an aorto-coronary bypass, pump-perfused at 50% of free flow, infusion of ALI into the bypass. The results showed that ALI iv dose-dependently reduced HR from 135/min to 90/min, LVedP rose from 8.6 to 10.0 mmHg and NISC-edL from 14.1 to 14.6 mm indicating increased ventricular filling. Non-ischemic systolic shortening did not change. Ischemic systolic shortening was improved from 9.2% to 17.5%, which was not due to an increase in RISC-edL (14.8 versus 14.7 mm), enhanced RISC-Q (13 versus 12 ml/min), reduced AoP (86 versus 84 mmHg) or change in inotropy (dP/dtmax: 2290 versus 2240 mmhg/s), but the increase in RISC-sdl correlated closely (r greater than 0.85) to the reduction in HR (oxygen-demand).(ABSTRACT TRUNCATED AT 250 WORDS)

Experience with anatomical correction of transposition of the great arteries (TGA).

During the past seven years, 102 patients with TGA have been operated on using the switch operation. Overall early mortality was 5.9%, late mortality 2.%. Sixty-three newborns had an intact septum and were corrected between the 3th and 35th day after birth, 39 had a ventricular septal defect and/or associated anomalies. All operations were carried out under ECC and deep hypothermia. Myocardial function was recorded intraoperatively by using sonomicrometry. The data demonstrate that adaptation of the left ventricle to the new load conditions should be supported by drugs providing inotropic stimulation and afterload reduction. Mean follow-up time is 32.5 months, no rhythm problems have been recorded during that period, a few children revealed trivial pulmonary or aortic valve stenosis and/or incompetence. The switch operation permits good early results for newborns with TGA and intact septum and TGA with VSD. A decade has to pass in order to judge the long-term results.

Relation between epicardial electrograms and signal-averaged electrocardiograms after acute myocardial infarction in dogs.

Signal-averaged electrocardiograms allow the non-invasive detection of late potentials which represent locally delayed conduction in the myocardium. To validate this method, it is necessary to compare the signal-averaged data with electrograms recorded directly from the heart. However, the studies performed to date involve only a consecutive collection of the invasively and non-invasively obtained data. To obtain a more direct comparison, we examined this relation at operation by simultaneous epicardial and signal-averaged measurements. Acute infarction in animals was chosen, because the ischemic area is a zone of delayed conduction whose presence can be verified in a signal-averaged electrocardiogram. For this purpose, the left anterior descending artery, proximal of large septal and diagonal branches, was tied off in nine mongrel dogs after thoracotomy. Before infarction, a signal-averaged electrocardiogram was recorded from the body surface. At the same time, epicardial electrograms were performed using bipolar electrodes both from the supply area of the left anterior descending artery and from that of the circumflex artery. Five minutes after coronary ligation, both the epicardial measurements and the signal-averaged electrocardiogram were repeated on the open thorax. Before occlusion of the left anterior descending artery, narrow activation complexes occurred in general in the epicardial electrograms and no late potentials were recorded in any dog by the signal-averaged electrocardiogram. Five minutes after coronary ligation, fractionated and prolonged electrograms occurred in the epicardial recordings from the ischemic zone, while the activation complexes in the uninfarcted supply area of the circumflex artery remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Models of coronary artery disease: "critical" versus "functional" coronary artery stenosis.

"Critical coronary stenosis" (reduction of coronary blood flow [Q] until reactive hyperaemia following 15s coronary occlusion is just abolished) and "functional stenosis" (reduction of Q until systolic shortening (dL) of post-stenotic myocardium is curtailed by 50%) were compared with respect to the reduction in Q necessary and the effect on regional myocardial and global ventricular function. In 9 anaesthetized (piritramide) dogs, enddiastolic length (edL) and dL of a myocardial area supplied by the left descending coronary artery (LAD) were measured by sonomicrometry. Left-ventricular end-diastolic pressure (LVEDP) and dP/dt, aortic pressure (AoP), stroke volume (SV), and heart rate (HR) were monitored. QLAD was stepwise reduced by a snare. Critical stenosis, present at a 25% reduction of QLAD, had no effect on regional and global ventricular function, but recovery of dL after release of 15s LAD occlusion was significantly delayed. Further obstruction of QLAD progressively impaired dL, reaching 50% dL (functional stenosis) by a flow reduction of about 50%. The decrease in dL was accompanied by an increase in edL. The haemodynamic effects of the functional stenosis were rather discrete (LVEDP + 5%, SV-12%, dP/dtmax-8%). Models of myocardial ischaemia used to study the effect of drugs or other haemodynamically effective interventions should be able to show functional impairment as well as improvement of the ischaemic myocardium. The critical stenosis does not impair myocardial function and, consequently, a favourable influence on the function and, consequently, a favourable influence on the function of ischaemic myocardium by any intervention may not become evident. However, in the presence of a functional stenosis the change in systolic shortening of the ischaemic myocardium is a very sensitive response to any intervention which affects the energy balance of the ischaemic myocardium. Therefore, this model should be preferred.

Significance of the subvalvular apparatus for left-ventricular dimensions and systolic function: experimental replacement of the mitral valve.

To study the significance of the subvalvular apparatus for left-ventricular performance in mitral valve replacement, a new experimental model was developed. In 21 dogs St. Jude prostheses were implanted in the mitral position preserving the chordae tendineae and the papillary muscles by plicating and fixing the mitral leaflets with the prosthesis on the valvular annulus. Flexible steel wires were slung around the chordae tendineae of the anterior and the posterior papillary muscle separately and passed through the left ventricular wall via insulating plastic cannulas. Left-ventricular dimensions and global systolic function were measured during volume loading with blood before and after severance of the chordae tendineae by external application of electrocautery to the steel wires. Thus the heart continued beating without any interference following loss of the subvalvular apparatus. The external left ventricular diameters in the major and minor axis were determined by sonomicrometry. Left-ventricular systolic and diastolic pressures were measured by catheter tip manometers, stroke volume by electromagnetic measurements of flow in the ascending aorta. When the chordae tendineae had been cut, left-ventricular end-diastolic diameters in the major axis were increased ( + 2%), in the minor axis decreased (-1%) at any left-ventricular end-diastolic pressure. Systolic shortening of the major axis diameter was considerably reduced (20-27%) at any left-ventricular end-diastolic pressure following severance of the chordae tendineae. Significant increase of the systolic shortening in the minor axis diameter occurred at preload levels of 3-6 mmHg (15-8%), while at higher left-ventricular end-diastolic pressure of 7-8 mmHg no significant changes were present.(ABSTRACT TRUNCATED AT 250 WORDS)