Performance of allografts and xenografts for right ventricular outflow tract reconstruction.

BACKGROUND: We compared the long-term durability of allografts and xenografts implanted for reconstruction of the right ventricular outflow tract. METHODS: A total of 401 patients were studied from January 1974 to June 2000 (145 xeno- and 256 allografts), follow-up being 98% complete. We analyzed freedom from reoperation and allograft specific factors that may indicate degeneration. RESULTS: The age at implantation was 2 days to 31 years (median 4.0 years). Conduit exchange rate was similar (p = 0.2) for conduit diameters less than 15 mm (41%+/-9% for allografts, 30%+/-6% for xenografts), but significantly different (p = 0.02) for diameters of 15 mm or larger (60%+/-8% for allografts, 30%+/-10% for xenografts). Diagnosis-related 20-year survival analysis showed a significantly (p = 0.01) better survival of patients with tetralogy of Fallot/pulmonary atresia (83%+/-5%) and Rastelli-type surgery (81%+/-8%) compared with patients with truncus arteriosus communis (69%+/-8%). ABO-compatibility, preservation method, and aortic or pulmonary allograft could not be identified as risk factors for allograft longevity. CONCLUSIONS: For smaller diameters (less than 15 mm), allografts exhibit no advantage over xenografts, whereas in larger diameters (15 mm or larger) allografts are the conduit of choice for the right ventricular outflow tract.

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.

Reconstruction of the RVOT with valved biological conduits: 25 years experience with allografts and xenografts.

OBJECTIVE: The reconstruction of the RVOT in congenital heart disease often requires the implantation of a valved conduit. Although allografts are considered the conduit of choice their availability is limited and therefore xenografts are implanted as well. We compared the long-term durability of both grafts in the RVOT over a 25-year period. METHODS: Between January 1974 and August 1999, 505 patients (median age 4.0 years, range 2 days-31 years; median weight 14.5 kg, range 2.2-76.6 kg; median body length 103 cm, range 48-183 cm) with congenital malformations (PA 25.3%, TOF 14.5%, TOF+PA 2.4%, DORV 4.2%, TGA+PS 8.7%, TAC 24.8%, and other 20.2%) received their first valved conduit (174 xenografts: median diameter 14 mm, range 8-27 mm; 331 allografts: median diameter 19 mm, range 8-30 mm). RESULTS: Follow-up is 3017 patient-years. The 10-year survival-probability for all patients. was 66% with a mean reoperation-free interval for conduit-exchange of 13.3 years (mean reoperation-free interval for allografts, 16.0 years; mean reoperation-free interval for xenograft, 10.3 years). One hundred and thirteen patients underwent a conduit-exchange, mostly due to conduit stenosis. Fourteen patients had a second exchange and three patients a third exchange. For patients with conduit diameters <18 mm (n=235: allograft n=116, xenograft n=119; median age 9 months, range 0-27.3 years), the mean reoperation-free interval was 11.2 years (mean interval allograft, 13.1 years; mean interval xenograft, 8.6 years, P=0.03). For conduit diameters >/=18 mm (n=270: allograft n=215, xenograft n=55, median age 7.4 years, range 0-34.3 years) the mean interval from freedom of conduit exchange was 15.1 years (for allografts 14.1 years, for xenografts 12.5 years, P<0.01). Comparing xenografts to allografts, we found no difference in patient survival probability (P=0.62). There was no significant difference between antibiotic (n=198) preserved vs. cryopreserved (n=133) allografts (P=0.06). Blood group compatibility of allografts to recipients had no significant influence on allograft function (P=0.42). The donors allograft origin, whether aortic or pulmonary valve, had also no significant influence on allograft long-term function (P=0.15). CONCLUSION: For the reconstruction of the right ventricular outflow tract (RVOT) allografts show significantly better long-term durability than xenografts regardless of the age at implantation and the diameter.

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.

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.

Endothelial prostacyclin (PGI-2) production of human and porcine valve allografts related to ischemic history.

BACKGROUND: The significance of cellular viability in human valve allografts for functional clinical longevity continues to be debated. Meaningful tests for this biological entity are therefore in demand to quantify the relative merits of graft origin and procurement techniques. The valve leaflet endothelium is recognized as a particularly sensitive target to noxes and its continued ability to produce prostacyclin (PGI-2) after explantation has been suggested as indicating viability. OBJECTIVE: Graft ischemic history and species differences were therefore studied in human and porcine valve leaflets by the measurement of endothelial prostacyclin production, post-explantational, basal and after stimulation with bradykinin. METHODS: Four groups of aortic valve donors were established. Fresh human heart-beating donors (h-HBD), cadaveric human donors (h-NHBD) processed within 24 h, fresh porcine donors (p-HBD) and cadaveric porcine donors (p-NHBD) also processed within 24 h. Leaflets were separately incubated at 37 degrees C for successive periods of 30 min up to 5 h in Earle's Medium 199. After 240 min PGI-2 production was stimulated by 10 microM bradykinin. Postincubational release was stopped with indomethacin 10 microg/ml. Prostacyclin production was measured as 6-kPGF1a using an ELISA. RESULTS: Initial PGI-2 production is significantly higher in porcine than in human grafts and in both species enhanced by previous warm ischemia. While baseline species differences disappear during progressive incubation, differences resulting from graft history are maintained. After PGI-2 stimulation species differences dominate again while ischemic history has no effect. CONCLUSION: Ischemia and surgical manipulation are stimulators of endothelial PGI-2 production in both human and porcine allografts and, therefore, a correlation of this metabolic activity with cellular integrity may be misleading. Valid data are obtained only if the natural time-course and reaction to stimulation of PGI-2 production are duely recognized and species differences in the response to mechanical and ischemic stress are considered.

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.

Allograft implantation in pediatric cardiac surgery: surgical experience from 1982 to 1994.

Between July 1982 and April 1994, a total of 290 patients (median age 6.5 years, range 1 month to 32.1 years, 69 patients younger than 1 year) underwent repair of their cardiac malformation by insertion of an allograft. The diagnoses were truncus arteriosus communis (n = 78, 27.0%), tetralogy of Fallot (n = 59, 20.0%), pulmonary atresia (n = 72, 25.0%), double outlet right ventricle (n = 15, 5.0%), complex transposition of the great arteries plus pulmonary stenosis (n = 37, 13.0%), and others (n = 29, 10.0%). Either pulmonary (n = 69) or aortic (n = 221) cadaver allografts were implanted. Two hundred twenty-nine of the allografts were antibiotic preserved. Since January 1991 (n = 61), a new cryopreservation procedure was employed for standardized uniform cooling using heat sinks and defined package geometry. Follow-up was complete for 95.2% (n = 276, 1,320 patient-years). Thirty-day mortality was 9.0% (n = 26) and late mortality was 12.1% (n = 35). Kaplan-Meier analysis revealed that patient survival was determined mainly by their underlying cardiac disease. All allografts with valve sizes less than 15.0 mm had to be exchanged within 7 years as these patients had outgrown their conduits. When the allograft was larger than 15.0 mm, exchange was necessary in 20% at 10 years. ABO compatibility and aortic or pulmonary origin of the allograft were not significant influences on allograft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Seal-less centrifugal blood pump with magnetically suspended rotor: rot-a-flot.

Limitations of current centrifugal blood pumps are related to heat generation of bearings and leakage of seals, to dead water zones, and to poor efficiency. A new concept is proposed in this paper to ameliorate these problems based on a miniaturized magnetic drive, and a prototype is introduced. The pump rotor is suspended and driven by a radial permanent magnetic field that stabilizes the impeller in 4 of the 6 spatial degrees of freedom and allows it to be top-spun on a single blood-flushed pivot bearing with minimal load and friction. A shrouded impeller with an open center and 4 logarithmically curved channels is run inside a cone-and-plate-type housing with a spiral volute chamber. In vitro testing was performed comparing this design with the BioMedicus, St. Jude, and Sarns pumps. The prototype is demonstrated to have the smallest internal volume (35 ml), surface (190 qcm), and passage time (0.5 s at 4 L/min), as well as the highest hydraulic efficiency (up to 0.4) of all devices studied.

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)

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)

Global and regional ventricular function following intracoronary application of papaverine.

Intracoronary injection of papaverine is used to determine coronary flow reserve in patients. The present study was to investigate the effect of papaverine on the performance of myocardium with reduced flow reserve. In nine anaesthetized open-chest dogs a bypass from the aorta to the left circumflex coronary artery (LCX) was established. Left ventricular end-diastolic and aortic pressure, dP/dt, stroke volume, LCX blood flow, and ECG were monitored. The performance of a segment of subendocardial wall supplied by the LCX was assessed by sonomicrometry. Peak reactive hyperaemia after 15s bypass occlusion was 1.44 +/- 0.09 times the baseline flow (41 ml/min), indicating reduced coronary flow reserve. Papaverine was injected into the bypass (0.3, 0.6, 1.2, 2.5, 5.0 mg/ml, 1 ml in 15s). The maximum LCX flow following PAPA 0.3 mg was comparable to peak reactive hyperaemia, but 10-15% higher after injection of 0.6-5.0 mg papaverine. Systolic shortening of the myocardium (control: 17.5% of end-diastolic length) became reduced in a dose-dependent fashion (5-25%) for about 1 min following papaverine injection. Stroke volume (control: 0.94 +/- 0.12 ml/kg) was reduced by about 8%, left ventricular end-diastolic pressure (control: 6.2 +/- 0.8 mmHg) increased by 15%, and dP/dtmin (control: 1850 +/- 150 mmHg/s) was curtailed by 15-25%. The ECG showed a transient T inversion and S-T depression following papaverine administration and in one experiment ventricular fibrillation occurred after the injection of 2.5 mg papaverine. The observed effects of intracoronary papaverine are consistent with the theory of transient subendocardial ischaemia arising from a redistribution of blood flow from the subendocardial to the subepicardial layers, because of greater vasodilatory capacity in the latter than in the former.