Successful management of MRSA sepsis in a patient with left ventricular assist device.

Left ventricular assist devices (LVADs) offer the opportunity to substantially improve the clinical conditions and to interrupt hospitalization of patients suffering from end-stage heart failure awaiting heart transplantation. The authors report a case of a 66-year old patient suffering from end-stage idiopathic dilative cardiomyopathy who needed the implantation of a LVAD and later developed a sepsis with a methicillin resistant Staphylococcus aureus (MRSA) which could be recovered by a differentiated antibiotic regimen.

Diastolic filling pattern and left ventricular diameter predict response and prognosis after cardiac resynchronisation therapy.

OBJECTIVE: To investigate predisposing factors for cardiac resynchronisation therapy (CRT) response. DESIGN: Single-centre study. SETTING: University hospital in Germany. PATIENTS: 122 consecutive patients with heart failure (mean (SD) age 65 (11) years; ischaemic/non-ischaemic 41%/55%; New York Heart Association (NYHA) class 3.1 (0.3); left ventricular ejection fraction 24.4 (8.1)%; QRS width 170 (32) ms, quality of life (QoL) 43.5 (19.2)) with an indication for CRT and demonstrated left ventricular dyssynchrony by echocardiography including tissue Doppler imaging. INTERVENTIONS: Besides laboratory testing of clinical variables, results of ECG, echocardiography including tissue Doppler imaging, invasive haemodynamics, measures of QoL and of exercise capacity were obtained before CRT implantation and during follow-up. MAIN OUTCOME MEASURE: Responders were predefined as patients with improvement by one or more NYHA functional class or reduction of left ventricular end-systolic volume by 10% or more during follow-up. Mean (SD) follow-up was 418 (350) days. RESULTS: Overall, 70.5% of patients responded to CRT. Responders had a significantly improved survival compared with non-responders (96.2% vs 45.5%, log-rank p<0.001). On univariate analysis, left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), E/A ratio, a restrictive filling pattern, mean pulmonary artery pressure, pulmonary capillary pressure, N-terminal pro-brain natriuretic peptide and Vo(2)max were significant predictors of outcome. On multivariate analyses, LVESD (p = 0.009; F = 7.83), pulmonary capillary pressure (p = 0.015, F = 6.61) and a restrictive filling pattern (p = 0.026, F = 5.707) remained significant predictors of response. CONCLUSIONS: Despite treatment according to present guidelines nearly 30% of patients had no benefit from CRT treatment in a clinical setting. On multivariate analyses, patients with an increased left ventricular end-systolic diameter and concomitant diastolic dysfunction had a significantly worse outcome.

Interference with cardiac pacemakers by magnetic resonance imaging: are there irreversible changes at 0.5 Tesla?

The safety and feasibility of magnetic resonance imaging (MRI) in patients with cardiac pacemakers is an issue of gaining significance. The effect of MRI on patients' pacemaker systems has only been analyzed retrospectively in some case reports. Therefore, this study prospectively investigated if MRI causes irreversible changes in patients' pacemaker systems. The effect of MRI at 0.5 Tesla on sensing and stimulation thresholds, lead impedance and battery voltage, current, and impedance was estimated during 34 MRI examinations in 32 patients with implanted pacemakers. After measurements at baseline and with documentation of intrinsic rhythm and modification of the pacing mode, patients underwent MRI. The rest of the function time of the pacemaker was calculated. Measurements were again performed after 99.5 +/- 29.6 minutes (mean +/- SD), immediately after MRI examination, and 3 months later. Lead impedance and sensing and stimulation thresholds did not change after MRI. Battery voltage decreased immediately after MRI and recovered 3 months later. Battery current and impedance tended to increase. The calculated rest of function time did not change immediately after MRI. MRI affected neither pacemaker programmed data, nor the ability to interrogate, program, or use telemetry. Surprisingly, in the gantry of the scanner, temporary deactivation of the reed switch occurred in 12 of 32 patients when positioned in the center of the magnetic field. Missing activation of the reed switch through the static magnetic field at 0.5 Tesla is not unusual. MRI at 0.5 Tesla does not cause irreversible changes in patients' pacemaker systems.

[MRI study of left ventricular function in patients with coronary disease and myocardial dysfunction before and after coronary revascularization]. / MR-tomographische Untersuchung der linksventrikulären Funktion bei Patienten mit koronarer Herzerkrankung und myokardialer Dysfunktion vor und nach koronarchirurgischer Revaskularisation.

PURPOSE: To evaluate left ventricular (LV) myocardial function in ten patients with coronary artery disease (CAD) preoperatively and 6 months after coronary bypass grafting (CABG) by cardiac MRI. MATERIAL AND METHODS: Ten patients (mean 65.2 +/- 5.9 years) with angiographically proven CAD and an indication for elective CABG underwent prospective evaluation of global LV function and regional wall motion by Cine-MRI at rest using a multiphase FLASH-2D sequence following regions of interest (ROI)-defined diagnostics of regional myocardial wall motion by means of levocardiography. Within the ROIs a total of 613 LV myocardial segments were analyzed preceding and following surgical revascularization. Results were compared with the data of 10 healthy volunteers. RESULTS: Preoperatively, patients showed reduced stroke volume and ejection fraction compared with volunteers (p < 0.01). Enddiastolic wall thickness (EDWT) and systolic wall thickening (SWT) were significantly lower in the patients (p < 0.01). Based on preoperative levocardiography ROI-defined myocardial segments showed a significantly lower preoperative EDWT in areas with wall motion abnormalities (7.4 +/- 2.5 mm; p < 0.01) than in normal myocardium (9.2 +/- 2.1 mm). Ejection fraction (p < 0.05), endsystolic wall thickness, and SWT (p < 0.01) improved significantly after bypass surgery. On ROI-defined analysis myocardial segments with impaired preoperative wall motion (n = 243) showed a significant increase of EDWT, ESWT and SWT (p < 0.01). CONCLUSION: In patients with CAD, cardiac MRI enables the non-invasive determination of postinfarctional LV remodeling with an increased EDWT of myocardial segments with normal regional wall motion and of the improvement in global and regional myocardial function following coronary bypass surgery.

Signal characteristics of multichannel epicardial electrograms in chronic ischaemic and scarred myocardium: electromechanical mismatch indicates viability in regions of myocardial dysfunction.

BACKGROUND: To predict the outcome after myocardial revascularisation, a clear separation between hibernation and/or repetitive stunning on the one hand and myocardial scarring on the other hand is of importance. METHODS AND RESULTS: A total of 44 patients was included in this study. In 35 patients with chronic myocardial ischaemia and an indication for coronary bypass-surgery, epicardial mapping of local activation was performed. Nine patients with LV aneurysm and an indication for antitachycardia surgery were also included. For simultaneous recording of the local electrograms during sinus rhythm, a sock electrode with 102 bipolar leads was used. The regional myocardial contraction pattern was assessed from preoperative angiograms and regional myocardial metabolism (viability) from 18F-FDG PET, respectively. The results were projected on the grid of the intraoperative position of the sock electrode. This enabled regional comparison of electrogram characteristics to local contraction patterns and viability. For the characterisation of local electrograms, peak-to-peak amplitude and duration of activation were calculated using custom-made automated computer-algorithms. Dysfunctional but viable areas showed normal or almost normal electrographic signal characteristics. In contrast, dysfunctional and non-viable myocardium showed a distinct reduction of local amplitudes and prolongation of signal duration. These changes were even more intense in areas of LV aneurysms. CONCLUSIONS: In patients with chronic ischaemic myocardium, a mismatch between mechanical function and local electrogram characteristics was observed in areas with preserved metabolism. Thus, normal epicardial electrograms in regions of myocardial dysfunction may be an indicator for myocardial viability.

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Are microbubbles free flowing tracers through the Myocardium? Comparison of indicator-dilution curves obtained from dye dilution and echo contrast using harmonic power Doppler imaging.

BACKGROUND: Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. METHODS AND RESULTS: A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. CONCLUSIONS: We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.

MR imaging and cardiac pacemakers: in-vitro evaluation and in-vivo studies in 51 patients at 0.5 T.

PURPOSE: To evaluate the safety and feasibility of magnetic resonance (MR) imaging at 0.5 T in patients with implanted cardiac pacemakers. MATERIALS AND METHODS: Twenty-one models of pacemakers and 44 pacemaker electrodes were exposed to in vitro MR imaging with continuous registration of pacemaker output and temperature at the lead tip. Prior to MR imaging examination, pacemakers were programmed to an asynchronous mode (A00, V00, or D00). Pacemakers were examined before and after MR imaging. Forty-four patients with implanted pacemakers underwent 51 MR imaging examinations under cardiologic surveillance, continuous electrocardiography, pulse oximetry, and capnographic monitoring. RESULTS: MR imaging was safely performed in all patients. None of the pacemakers displayed a pacing dysfunction at MR imaging. No changes occurred in the programmed parameters in any device tested in vivo or in vitro. Maximum increases in the temperature at the lead tips were 8.90 degrees C at a specific absorption rate (SAR) of 0.6 W/kg and 23.50 degrees C under a worst-case radio-frequency (RF) heating condition with an SAR of 1.3 W/kg. CONCLUSION: MR imaging at 0.5 T can be safely performed in patients with implanted pacemakers in carefully selected clinical circumstances when appropriate strategies (programming to an asynchronous mode, adequate monitoring techniques, limited RF exposure) are used.

Predictors of success in radiofrequency catheter ablation of atrial flutter.

Radiofrequency catheter ablation of typical atrial flutter at the isthmus between the tricuspid annulus and the inferior vena cava is established. However in selected patients, the creation of a continuous linear lesion at the targeted isthmus requires a lengthened procedure or is not feasible at all and atrial flutter recurrences are common. In a retrospective analysis, we found that an intraoperatively determined distance between the tricuspid annulus and the inferior vena cava of <.2.5 cm is an independent predictor of a lengthened or failed ablation procedure. Additional equipment, e.g., long introducer sheaths, adapted ablation catheter design, or irrigated tip ablation, as well as alternative ablation approaches, e.g., linear lesions between the tricuspid annulus and Eustachian ridge, have been invented in order to increase the acute success rate or decrease fluoroscopy and procedure time. In a prospective study on the effects of various conduction properties at the isthmus between tricuspid annulus and inferior vena cava following radiofrequency ablation of atrial flutter, we showed previously that others than a complete bidirectional conduction block predicts a high recurrence rate of atrial flutter. For determination of transisthmal conduction properties following ablation, established mapping approaches are documentation of double potentials at the ablation line and right atrial activation sequence following posteroseptal and low lateral right atrial pacing. Novel threedimensional mapping systems, i.e., Carto(R) and EnSite(R), may further enhance the accuracy of conventional mapping techniques.

Clinical experience with implantable atrial and combined atrioventricular defibrillators.

UNLABELLED: The high prevalence of atrial fibrillation (AF) and its clinical complications, the poor efficacy of medical therapy for preventing recurrences, and dissatisfaction with alternative modes of therapy stimulated interest in implantable atrial and combined atrioventricular defibrillators. In a multicenter study, the safety and efficacy of a stand alone implantable atrial defibrillator, the Metrix system, were evaluated. The device was implanted in 51 patients with highly symptomatic episodes of AF refractory to pharmacological treatment. During a follow-up of 9 months, 96% of 227 spontaneous AF episodes were successfully converted to sinus rhythm in 41 patients. In 62 episodes (27%), several shocks and/or additional drug treatment were required to maintain stable sinus rhythm because of early recurrences of AF. A total of 3719 shocks were delivered and no induction of ventricular proarrhythmia or inaccurately synchronized shocks occurred. The AF detection algorithm exhibited a 100% specificity for the recognition of sinus rhythm and a 92.3% sensitivity for the detection of AF. The combined atrioventricular defibrillator, Jewel AF 7250, was evaluated in a multicenter, randomized, cross-over trial. The primary study objectives included: overall safety as determined by complications-free survival at 6 months, efficacy of tiered atrial pacing and defibrillation therapies for termination of spontaneous atrial tachycardias (AT) and AF, and relative sensitivity of a new dual-chamber detection algorithm. The device was implanted in 211 patients with either a history of ventricular tachyarrhythmias (VT/VF) alone or with a history of both AT/AF and VT/VF. During a mean follow-up of 4.5 months, it has been shown that the Jewel AF is safe and effective in treating atrial and ventricular tachyarrhythmias. Pace termination of 85% of AT episodes were achieved with painless delivery of antitachycardia pacing; additional 35% of AT episodes were terminated by high frequency burst pacing. CONCLUSIONS: The stand alone implantable atrial defibrillator may be safe and clinically useful in selected patients for the treatment of highly symptomatic, drug resistant recurrences of AF. The combined atrioventricular defibrillator may be particularly indicated in patients presenting with both a history of atrial and ventricular tachyarrhythmias.

[MRI diagnosis of cardiac myxomas: sequence evaluation and differential diagnosis]. / MRT-Diagnostik kardialer Myxome: Sequenzevaluierung und Differentialdiagnose.

PURPOSE: To evaluate native and contrast enhanced T1-weighted spin (T1-SE), cine gradient echo (Cine-GE), and T2-weighted turbo spin (T2-TSE) sequences in the diagnosis and differential diagnosis of cardiac myxomas. METHODS: 15 patients with echocardiographically suspected cardiac atrial myxomas underwent 0.5 T-MR imaging of the heart with native T1-SE, contrast-enhanced T1-SE, Cine-GE, and T2-TSE sequences. MR images were evaluated for signal intensity (SI) and lesion's conspicuity. Results were confirmed histologically (14 x) or by follow-up (1 x). RESULTS: MRI revealed myxomas in 9 patients, sarcomas in three patients, and thrombi in three patients. Lesion conspicuity was better in Cine-GE and T2-TSE compared with native and contrast-enhanced T1-SE sequences. Myxomas were characterized by an intermediate SI similar to myocardium in T1-SE, high SI similar to water in T2-TSE, and low to moderately high enhancement (range 19-75%, mean 48%). CONCLUSION: Distinct SI characteristics together with anatomical-topographical features (attachment to the interatrial septum, no infiltration of myocardium and vessels) are diagnostic for cardiac myxomas. Cine-GE and T2-TSE sequences are the sequences of choice for detection of myxomas and other atrial masses. T2-TSE and contrast-enhanced T1-weighted sequences are most useful for mass characterisation and differentiation between myxomas, malignant tumors, and thrombi.

Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation.

In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI) due to treatment with class IC antiarrhythmic drugs. In this study, we prospectively investigated the effects of AFI ablation and continuation of drug therapy in patients with AF who developed AFI due to long-term administration of class IC antiarrhythmic drugs. The study population consisted of 187 patients from an AF registry with paroxysmal AF who were orally treated with flecainide (n = 96) or propafenone (n = 91). Twenty-four patients (12.8%) developed AFI during the course of treatment. In 20 of these patients (10.7%), electrophysiologic study revealed typical AFI. These patients underwent radiofrequency ablation of AFI. Ablation failed in 1 patient. All patients continued preexisting drug treatment. Recurrence of AF was assessed by ambulatory Holter monitoring and serial questionnaires. During a mean follow-up of 11 +/- 4 months, the incidence of AF episodes was significantly lower in patients with a combined therapy (2.7 +/- 3.6 per year) than in control subjects with a sole drug treatment (7.8 +/- 9.2 per year, p <0.05) and than before therapy (10.2 +/- 5.4 per year, p <0.001). Subgroup analysis revealed that 7 patients (36.8%) remained symptom free with no evidence of atrial tachyarrhythmia. Eight additional patients (42.1%) had ongoing paroxysmal AF, however, with a significantly lower incidence of AF episodes than before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It is concluded that in patients with AF who develop typical AFI due to administration of class IC antiarrhythmic agents, a combined therapy with catheter ablation of AFI and continuation of drug treatment is highly effective in reducing occurrence and duration of atrial tachyarrhythmias.

Unique cardioprotective action of the new calcium antagonist mibefradil.

BACKGROUND: Mibefradil is a calcium antagonist with few negative inotropic effects at therapeutic concentrations. METHODS AND RESULTS: The effect of mibefradil on infarct size (IS) was compared with those of placebo, amlodipine, and verapamil in 64 anesthetized pigs. In placebo pigs, after 90 minutes of ischemia and 120 minutes of reperfusion, IS (by triphenyl tetrazolium chloride staining) was 15.3+/-10.8% (SD) of the area at risk. Mibefradil (0.60 mg/kg IV) reduced heart rate and left ventricular (LV) pressure, and IS was 1. 9+/-3.9% (P<0.05 versus placebo). Verapamil (0.15 mg/kg IV) also decreased heart rate, LV pressure, and IS (6.1+/-4.2%, P<0.05 versus placebo). Amlodipine (0.20 mg/kg IV) did not alter heart rate, LV pressure, or IS (9.9+/-5.4%, P=NS versus placebo). When heart rate was maintained constant by left atrial pacing and LV pressure was adjusted to that of the placebo group by an intra-aortic balloon, mibefradil still decreased IS (3.8+/-3.0%, P<0.05 versus placebo), but verapamil did not (11.6+/-8.3%, P=NS versus placebo). With glibenclamide infusion, mibefradil no longer reduced IS (13.1+/-4.3% versus 17.8+/-5.6% with glibenclamide alone, P=NS). CONCLUSIONS: The IS-limiting effect of mibefradil, in contrast to that of verapamil, was not dependent on favorable hemodynamics but was abolished by glibenclamide, suggesting a direct cardioprotective action of mibefradil.

Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats.

Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.

Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin.

BACKGROUND: A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. METHODS AND RESULTS: In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7+/-3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9+/-7.0%). IS was decreased to 9.0+/-2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9+/-0.9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573+/-144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 minutes of IPc but increased to a similar extent with 3 minutes (by 198+/-32%) and 10 minutes (by 224+/-30%) of IPc. The IS reduction by 3 minutes of IPc was abolished by blockade of the bradykinin B2 receptor with intracoronary HOE 140 (16.6+/-4.3%) but not with intracoronary infusion of adenosine deaminase (8.4+/-2.5%, P<0.05). HOE 140, however, did not affect the IS reduction (3.5+/- 1.1%, P<0.05) by 10 minutes of IPc. Combined infusion of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4+/-6.7%). CONCLUSIONS: IS reduction by IPc is a graded phenomenon. Whereas bradykinin is essential during preconditioning ischemia of shorter duration, adenosine is more important during preconditioning ischemia of longer duration.

Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs.

In rabbits, inhibition of either protein kinase C or protein tyrosine kinase abolishes the infarct size reduction achieved by ischemic preconditioning. In pigs, however, inhibition of protein kinase C does not attenuate ischemic preconditioning. The present study tested whether inhibition of protein tyrosine kinase alone or in combination with inhibition of protein kinase C interferes with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD was cannulated and perfused from an extracorporeal circuit. Protein tyrosine kinase and protein kinase C were inhibited by continuous intracoronary infusion of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively. Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was analysed by TTC staining (% of LV area at risk) following 90 min low-flow ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of 16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0. 01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine, infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01 ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01 ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by simultaneous inhibition of both, protein kinase C and protein tyrosine kinase, suggests a complex signal cascade involving both protein kinases.

Impact of resting and ischemic blood flow on infarct probability in ischemic preconditioning--a new approach to infarct size-blood flow data by logistic regression.

The linear regression analysis of infarct size (IS) v ischemic myocardial blood flow (MBF) does not account for the heterogeneity of MBF and infarcted tissue; moreover, it cannot assess a blood flow threshold for infarction (MBFT) accurately, as with ischemic preconditioning (IP) the close relationship between ischemic MBF and IS otherwise observed is lost. Finally, the impact of resting blood flow on myocardial infarction cannot be considered in such analysis. Therefore, in a retrospective data analysis of 32 enflurane-anaesthetized swine undergoing 90 min severe ischemia and 120 min reperfusion without (CON, n = 12) or with IP induced by either 3 (IP3, n = 8) or 10 min ischemia (IP10, n = 12) and 15 min reperfusion, a MBFT was assessed by logistic regression (LR) in individual tissue pieces. MBFT was arbitrarily defined as that ischemic MBF (microspheres) at which infarct probability was 0.2, derived from the ratio of infarcted (n = 141, TTC) to all tissue samples (n = 684). The duration of the preconditioning ischemia and MBF both at rest and during the sustained ischemia were significant predictors of infarct probability. Ischemic MBFT at an infarct probability of 0.2, was 0.089 +/- 0.023 ml/min/g in CON. MBFT was decreased to 0.051 +/- 0.03 ml/min/g with IP3 (P < 0.05 v CON) and further to 0.004 +/- 0.037 ml/min/g with IP10 (P < 0.05 v CON, IP3). Corresponding to the leftward shift of MBFT, the relationships between infarct probability and MBF were shifted in parallel by IP with no change in their slopes.

Association between hemodynamic parameters and the degeneration of sustained ventricular tachycardias into ventricular fibrillation in rats.

UNLABELLED: Sustained ventricular tachycardias (VT) often degenerate into ventricular fibrillation (VF). In the present study, the impact of VT on mean arterial blood pressure (MAP), myocardial blood flow (MBF), and myocardial oxygen consumption (MVCO2) was assessed. In addition, the degeneration of sustained VT into VF was analysed with respect to MAP. MBF was measured in 48 anesthetized rats with colored microspheres; arterial catecholamine levels were measured by HPLC in 16 additional rats during control conditions and VT. MBF (4. 66+/-1.29 ml/g/min; mean+/-s.d.) did not change with the onset of VT (5.37+/-1.92 ml/g/min, n.s.). Epinephrine (0.22+/-0.13 ng/ml) and norepinephrine (0.37+/-0.12 ng/ml) increased during VT (3.55+/-2.68 ng/ml, P<0.01; 0.88+/-0.44 ng/ml, P<0.05), respectively. VF was more frequent when MAP remained normal (MAP>80 mmHg: 26%) than with hypotension (MAP<80 mmHg: 2%, P<0.05). Mechanical failure was observed in 10% of rats with severe hypotension (MAP<60 mmHg), and 2% with moderate hypotension (MAP 60-80 mmHg). The endo-epicardial MBF ratio in the VF group was significantly lower than that in the non-VF group (0.94+/-0.17 v 1.11+/-0.24, P<0.05). CONCLUSIONS: severe hypotension predisposes to the occurrence of acute mechanical failure during VT; moderate hypotension during VT, however, serves as a protective mechanism against VF in structurally normal hearts. Subendocardial hypoperfusion in the presence of an increased energy demand during VT is suggested to be responsible for the initiation of VF.

No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine.

The delay of infarct size development by ischemic preconditioning involves the activation of protein kinase C in rats and rabbits. In dogs the role of protein kinase C in ischemic preconditioning is controversial. We investigated whether or not the activation of protein kinase C is a prerequisite for ischemic preconditioning in swine. Swine were used, since they are large mammals and since infarct development in this species, due to the lack of an innate collateral circulation, is similar to that in humans. In 20 enflurane-anesthetized swine, the proximal left anterior descending coronary artery was cannulated and perfused from an extracorporeal circuit. The impact of continuous intracoronary infusion of 10(-7) mol/L staurosporine, a potent protein kinase C inhibitor, on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres), and infarct size (IS, triphenyltetrazolium chloride staining after 120 minutes of reperfusion) was analyzed. Staurosporine (10(-7) mol/L) abolished the 1.6-fold increase in coronary arterial resistance in response to 10(-6) mol/L IC 4 beta-phorbol 12-myristate 13-acetate, a potent protein kinase C activator. In the presence of staurosporine, 90 minutes of low-flow ischemia at an ENDO of 0.05 +/- 0.04 (mean +/- SD) mL.min-1.g-1 resulted in an IS of 12.5 +/- 8.6% (n = 10) of the area at risk. Also, in the presence of staurosporine, ischemic preconditioning by a cycle of 10 minutes of low-flow ischemia followed by 15 minutes reperfusion before the 90 minutes sustained ischemic period (ENDO, 0.05 +/- 0.03 mL.min-1.g-1) reduced IS to 3.3 +/- 3.4% (n = 10, P < .05). The protein kinase C inhibitor staurosporine does not prevent ischemic preconditioning in swine.