Does adenosine pharmacologically precondition human myocardium during coronary bypass surgery?

AIM: Adenosine (Ado) triggers ischemic preconditioning. We investigated whether Ado provides additional myocardial protection in patients during intermittent aortic cross-clamping (IAC) bypass surgery. METHODS: The placebo group was made of 15 male of 66+/-8 years while the Ado group was made of 19 male of 65+/-10 years. The patients of the Ado group had a 3-vessel heart disease and were treated with elective surgery. With the aortic cross-clamping, Ado or vehicle were infused over 10 min at systemic pressure together with sufficient blood via the aortic root. Blood samples before anaesthesia and onset of ECC, 1 hour after end of surgery, and on day 1 and 2 post-surgery to assess CK-MB and troponin I were performed. Hemodynamic measures (heart rate, left ventricular pressure, max/min pressure rise, central venous pressure) before installation and 15 min after completion of the coronary artery bypass. Different ECGs for electrophysiological analyses were performed. RESULTS: Hemodynamic and laboratory measures revealed no significant advantages of either protocol. Mortality rate was zero in both groups. CONCLUSIONS: The comparable outcome is likely due to cardioprotection provided by both IAC bypass surgery and hypothermia, which might obscure beneficial effects of pharmacological preconditioning in patients with good left ventricular function (ejection fraction >50%). As the benefit might have been marginal, it may well become apparent in a larger study on patients with more severe left ventricular dysfunction.

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

OBJECTIVE: To amplify the description of myocardial stunning. DESIGN: Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS: 15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES: Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS: Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS: Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus.

Aortocoronary bypass grafting: a comparison of HTK cardioplegia vs. intermittent aortic cross-clamping.

OBJECTIVE: Intermittend, hypothermic aortic cross-clamping (IAC) with myocardial fibrillation and cardioplegic arrest (CA) have been established both as effective methods for coronary artery bypass surgery (CABG). Nevertheless, there exists controversy about the more beneficial cardioprotective effect of one of these procedures in CABG-patients. METHODS: In this prospective study we compared the clinical outcome, ischemic serum-markers (CK, CK-MB, Troponin I), electrocardiogram (ECG)-changes, and hemodynamic data of 103 patients. Randomization in group I (IAC; n=52) or group II (CA; n=51) was done consecutively, all data were compared by Student's t-test or chi(2)-test and P<0.05 was regarded as significant. The Bretschneider-HTK solution was used for cardioplegic arrest. Data were collected before operation, before ischemic arrest, after 5 and 60 min of reperfusion, 1 and 6 h after operation, 1, 2 and 10 days postoperatively. RESULTS: There were no significant differences between both groups regarding general patient data: age (IAC: 64. 8+/-9.2 vs. CA: 63.8+/-9.0 years), left ventricular function (ejection fraction: IAC: 62+/-14 vs. CA: 64+/-13%), the amount of bypassed vessels (IAC: 3.4+/-0.5 vs. CA: 3.6+/-0.5), total bypass time (IAC: 113+/-31 vs. CA 108+/-20 min). The total time of ischemia was significantly less in the IAC group with 37+/-10 vs. 48+/-10 min in the CA group. In the IAC-group, a higher mortality was noticed (7. 7 vs. 3.9%; N.S.). This was combined with a significantly higher amount of patients with peak serum-values of CK-MB (>40 U/l) and troponin I (>50 ng/ml), 17 in the IAC-group (33%) vs. eight in CA-group (16%). Cerebral strokes were seen in two IAC-patients and none in CA-patients (NS). ECG-changes occurred in 22 IAC patients (42%) vs. 16 CA patients (31%); persistent ischemia related ECG-changes in six IAC (11.5%) vs. five CA-patients (9.8%). CONCLUSIONS: Both cardioprotective methods, IAC and HTK-cardioplegia, seem to offer sufficient myocardial protection in normal CABG-procedures. Although neurologic disorders and mortality rates were higher in patients with intermittent aortic cross-clamping, the differences to the cardioplegia group were not significant. According to the analysis of increased ECG-changes, higher CK-MB and troponin I values, which occurred especially in patients with myocardial ischemia time longer than 40 min, we conclude that cardioplegic arrest with HTK seems to offer more beneficial effects in procedures with prolonged ischemia.

Myocardial efficiency in stunned myocardium. Comparison of Ca(2+)-sensitization and PDE III-inhibition on energy consumption.

OBJECTIVE: In stunned myocardium oxygen consumption is relatively high compared with the reduced ventricular function. On the other hand, inotropic stimulation is frequently required to improve postischemic ventricular dysfunction. However, inotropic agents which act via intracellular increased calcium result in a higher oxygen demand. Therefore Ca(2+)-sensitization might be a favorable alternative. METHODS: The effects of a novel Ca(2+)-sensitizer (EMD 60263, 10 microM, group 1) were compared with a phosphodiesterase (PDE) III-inhibitor (enoximon, 20 microM, group 2) on 14 isolated, blood-perfused rabbit hearts during reperfusion after a global ischemia of 20 min. Ventricular function, the pressure-volume area (PVA, a measure of total mechanical work), and total myocardial oxygen consumption (MVO(2)) were assessed. Contractile efficiency (EF(cont)), derived from the reciprocal of the slope of the MVO(2)-PVA relation, and external efficiency (EF(ex), stroke work/MVO(2)), were calculated. RESULTS: At matched heart rate (group 1: 141+/-10 min(-1) group 2: 151+/-28 min(-1)) and end-diastolic volume (1.3+/-0.2 ml) systolic variables were significantly decreased in stunned myocardium: LVP(max) to 57+/-13% of control value in group 1 and to 76+/-7% in group 2, aortic flow to 20+/-4 vs. 25+/-8%. PVA was decreased to 57+/-13 and 67+/-11%, MVO(2) was non-significantly decreased to 73+/-22 and 88+/-14%. After administration of either inotropic agent LVP(max) was significantly improved to 96+/-12 vs. 90+/-8% compared with preischemic levels, aortic flow to 103+/-24 vs. 88+/-9%, and PVA 99+/-11 vs. 89+/-16%, respectively. EMD 60263 increased MVO(2) to control levels (107+/-9%), and enoximon raised MVO(2) even more significantly above control (139+/-13%). Both myocardial efficiency indices were significantly diminished during reperfusion: EF(ex) to 14+/-9 vs. 23+/-7% and EF(cont) to 71+/-7 vs. 65+/-9% compared with preischemic levels. EF(ex) (109+/-21%) was significantly, but EF(cont) only slightly (84+/-11%) increased after administration of EMD 60263, whereas EF(ex) (57+/-13%) and EF(cont) (71+/-12%) remained depressed after enoximon. CONCLUSIONS: In stunned myocardium, the decreased efficiency indices show that energy utilization is disturbed. Both agents recruited an inotropic reserve, whereas Ca(2+)-sensitization seemed to be more favorable in terms of myocardial efficiency indices. These results indicate that alteration of myocardial calcium sensitivity contributes a major part to postischemic dysfunction. Therefore, Ca(2+)-sensitization may potentially be a superior method for inotropic support in the postischemic heart.

Left ventricular dysfunction and disturbed O(2)-utilization in stunned myocardium: influence of ischemic preconditioning.

OBJECTIVE: Myocardial dysfunction during postischemic reperfusion is frequently reported only in terms of left ventricular (LV) systolic properties. We additionally assessed diastolic properties, the cardiovascular tone and in particular, the relation between ventricular function and myocardial oxygen consumption. Moreover, these measures are investigated after cardioprotection via ischemic preconditioning (IP). However, this phenomenon is not fully understood, and therefore cardioprotective methods like ischemic preconditioning might provide only insufficient protection. METHODS: In a total of 17 isolated rabbit hearts, perfused with an erythrocyte suspension (Hct 30%), we investigated the effect of 20 min low-flow ischemia also on diastolic properties, coronary resistance and cardiac energetics (n=9). During control and 30 min after the onset of reperfusion, LV systolic function was assessed in terms of aortic flow, dP/dt(max) and the end-systolic pressure-volume relation (ESPVR). Early relaxation was evaluated via dP/dt(min) and diastolic properties were assessed via the end-diastolic pressure-volume relation (EDPVR), i.e. using the equation LVP(ed)=c.exp(m.LVV(ed)), where c equals the LVP(ed)-axis intercept and m equals LV stiffness. In addition, coronary resistance (R(cor)) and the pressure-volume area (PVA) were calculated. Total oxygen consumption (MVO(2)) was calculated as well as the contractile efficiency (E = inverse slope of the MVO(2)-PVA relation). In a second series (n=8) the effect of ischemic preconditioning (3 min no-flow and 8 min reperfusion before the 20 min low-flow ischemia) was tested. RESULTS: In the first series, systolic function was impaired during reperfusion: aortic flow to 32% of control, dP/dt(max) to 74% and the slope of ESPVR to 73%. Early relaxation in terms of dP/dt(min) decreased to 76%. The slope of the EDPVR was steeper in stunned myocardium with an increase of the ventricular stiffness (m increased from 3.2 to 4.1) and with an upward shift of the EDPVR (c from 0.6 to 2.4 mmHg). Coronary resistance was increased (from 0.9 to 1.4 mmHg/ml per min) and PVA was significantly decreased to 68%, whereas MVO(2) was not, indicating also a decrease in contractile efficiency E from 28 to 14%. In the second series, recovery of systolic function was significantly improved by IP compared with the first series (aortic flow 56% of preischemic control, dP/dt(max) to 91% and ESPVR to 78%). LV stiffness m was also slightly increased from 3.1 to 3.9 and again, c was elevated, indicating no beneficial effect for diastolic properties including dP/dt(min) (77%). But IP improved R(cor) significantly (from 0.9 to only 1.0 mmHg/ml per min) and efficiency E to 21% (from 27% during control). CONCLUSION: Brief episodes of ischemia not only induce systolic but also diastolic and vascular stunning at almost maintained MVO(2). The decreased contractile efficiency clearly indicates an impaired O(2)-utilization of the contractile apparatus. Ischemic preconditioning did not improve diastolic function during reperfusion, but it provided protection with respect to vascular stunning and myocardial energetics.

Heart-type fatty acid binding protein (hFABP) in the diagnosis of myocardial damage in coronary artery bypass grafting.

OBJECTIVES: Heart-type fatty acid binding protein (hFABP) is an intracellular molecule engaged in the transport of fatty acids through myocardial cytoplasm and has been used as a rapid marker of myocardial infarction. However, its value in the evaluation of perioperative myocardial injury has not yet been assessed. METHODS: 32 consecutive patients undergoing coronary artery bypass grafting were included in a prospective, randomized study using standardized operative procedures and myocardial protection. Three patients with perioperative myocardial infarction were added. Serial blood samples were taken preoperatively, before ischemia, 5 and 60 min after declamping, 1 and 6 h postoperatively and on postoperative days 1, 2 and 10 and were tested for hFABP, creatine kinase isoenzyme MB (CKMB) and troponin I (TnI). RESULTS: Hospital mortality was zero. The kinetics of the biochemical parameters revealed a typical pattern for each marker. In routine patients, hFABP levels peaked as early as 1 h after declamping, whereas CKMB and TnI peaked only 1 h after arrival in the intensive care unit. Patients with perioperative infarction displayed peak levels some hours later in all marker proteins. Peak serum levels of hFABP correlated significantly with peak levels of CKMB (r=0.436, P=0.011) and TnI (r=0.548, P=0.001), indicating the degree of myocardial damage. CONCLUSIONS: hFABP is a rapid marker of perioperative myocardial damage and peaks earlier than CKMB or TnI. The kinetics of marker proteins in serial samples immediately after reperfusion is more suitable for the detection of perioperative myocardial infarction than a fixed cut-off level.

Effect of changes in aortic pressure and in coronary arterial pressure on left ventricular geometry and function Anrep vs. gardenhose effect.

Sudden increases in aortic pressure (AoP, mm Hg) are associated with increases in left ventricular (LV) function which persist even after diastolic volume has returned to its initial value (Anrep effect). Likewise, increases in coronary arterial pressure (CAP, mm Hg) are associated with improved LV function (gardenhouse effect). In situ, increases in AoP are paralleled by increases in both CAP and coronary blood flow, i.e., oxygen supply. We investigated the individual contributions of AoP and CAP increases on function (peak systolic pressure: LVPmax, mm Hg; dP/dtmax, mm Hg/s; end-diastolic pressure: LVPed, mm Hg) and end-diastolic geometry (inner diameter: IDed, mm; wall thickness: WTed, mm; sonomicrometry). CAP-induced increases in coronary flow were prevented by admixing dextran to the perfusate. The experiments were performed on isolated, saline-perfused, working rabbit hearts. Increasing CAP from 60 to 80 mm Hg (n = 11) resulted in improved function: LVPmax 89 +/- 3 vs. 94 +/- 3, dP/dtmax 1160 +/- 50 vs. 1250 +/- 50, LVPed 17 +/- 1 vs. 16 +/- 1 (mean +/- SEM). IDed decreased from 9.96 +/- 0.25 to 9.64 +/- 0.33 and WTed increased from 6.02 +/- 0.16 to 6.15 +/- 0.17. In a second series, AoP was increased from 60 to 80 (n = 9). Both LVPmax, dP/dtmax and LVPed increased (90 +/- 4 vs. 97 +/- 3, 1170 +/- 70 vs. 1270 +/- 90 and 18 +/- 1 vs. 19 +/- 1). IDed increased from 9.76 +/- 0.39 to 9.99 +/- 0.37 and WTed decreased from 6.08 +/- 0.22 to 5.86 +/- 0.25. After additionally increasing CAP to 80, function further improved (LVPmax: 101 +/- 3, dP/dtmax: 1310 +/- 80) while LVPed decreased (18 +/- 1). This time, IDed decreased to 9.71 +/- 0.36 and WTed increased to 6.03 +/- 0.26. Increases in CAP improve LV function via the gardenhose effect and likely do not depend on simultaneous increases in coronary flow or oxygen supply. On the other hand, increases in AoP alone improve systolic function via the Frank-Starling mechanism. Increases in both pressures together amplify this effect. Increases in CAP and in AoP have opposing effects on IDed and WTed. In conclusion, the homeometric Anrep effect--at least in part--can be viewed as synergistic action of the Frank-Starling mechanism and the gardenhose effect for this experimental model.

[The value of CKMB and myoglobin determinations during reperfusion after regional myocardial ischemia in the anesthesized pig]. / De Wert von CKMB- und Myoglobin-Bestimmungen währen Reperfusion nach regionaler Myokardischämie am narkotisierten Schwein.

The efficacy of a revascularization treatment after acute coronary artery occlusion can be evaluated by different diagnoses. The ECG and the time-course of, for example, the CK isoenzyme MB are widely used as quick, objective, and almost noninvasive tools. In addition, the assessment of functional recovery of the postischemic myocardium or the evaluation of the magnitude of irreversibly injured myocardium is essential for therapeutic strategies. In the present study, myoglobin that is not yet routinely established, is compared with CKMB to answer the following questions: do measurements of serum-CKMB and serum-myoglobin reliably demonstrate 1) the success of a revascularization treatment? 2) the functional recovery of the postischemic myocardium? 3) the magnitude of irreversibly injured myocardium? To answer these questions, the left anterior descending coronary arteries of 17 anesthetized pigs were occluded for 60 min and reperfused for 180 min after successful "revascularization". The major findings of this study on anesthetized pigs are: 1) The time-course of both the CKMB activity and the myoglobin concentration exhibit the successful revascularization. 2) The CKMB maximum does not exhibit the recovery of the ventricular function, whereas the myoglobin maximum moderately correlated with the contractile state (dP/dtmax) at the end of reperfusion and significantly with the recovery of dP/dtmax during reperfusion. Recovery of the regional function (= mean thickening velocity) within the 180 min reperfusion is predicted neither by CKMB nor myoglobin analysis. 3) Both investigated markers correlate closely with the magnitude of the irreversibly injured myocardium.

Comparison between the effects of a novel Ca++ sensitizer and a phosphodiesterase inhibitor on stunned myocardium.

Inotropic agents are used widely for pharmacological bridging of the failing heart either until recovery after surgical intervention or until transplantation. EMD 57033 is a novel specific Ca++ sensitizing agent with purportedly minor phosphodiesterase (PDE) III-inhibiting properties. It acts as an inotropic agent without raising intracellular Ca++ levels. In turn, the PDE III-inhibitor enoximone has been used for several years to treat low cardiac output syndrome. However, little is known about its effects on postischemic reperfused (stunned) myocardium. We investigated the effects of EMD 57033 (EMD; 30 microM) and enoximone (E20 micrograms/ml) on stunned myocardium. The experiments were performed on 16 isolated rabbit hearts perfused with an erythrocyte suspension (hematocrit = 30%; [Ca++] = 2.5 mM). Hearts were reperfused after a 20 min no-flow ischemia. Measurements were performed at control, 30 min after the onset of reperfusion, and after administration of one of the drugs. Both agents significantly improved the depressed systolic function [left ventricular pressure (LVP)max from 61 +/- 12 to 93 +/- 18 mmHg, and its derived pressure (dP/dt)max from 860 +/- 220 to 1340 +/- 300 mmHg/s and LVPmax from 78 +/- 9 to 83 +/- 15 mmHg, and its derivative dP/dtmax from 1040 +/- 230 to 1385 +/- 300 mmHg/s, respectively] and early relaxation (dP/dtmin from 810 +/- 250 to 1260 +/- 345 mmHg/s and from 1000 +/- 200 to 1135 +/- 295 mmHg/s, respectively) that occurred during postischemic reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of oxygen by the contractile apparatus is disturbed during reperfusion of post-ischaemic myocardium.

UNLABELLED: Post-ischaemic ventricular function remains depressed (= myocardial stunning) despite nearly normal coronary blood flow during reperfusion. In order to illuminate the causes of this phenomenon, we studied the relationship between ventricular function and myocardial oxygen consumption (MVO2tot) in experiments on 15 isolated rabbit hearts perfused with erythrocyte suspension (hct = 30%). Left ventricular systolic function was assessed by measuring aortic flow (ml.min-1), peak systolic pressure (LVPmax), dP/dtmax, and early relaxation in terms of dP/dtmin during control and 30 min after the onset of reperfusion, following 20 min global no-flow ischaemia. The pressure-volume area was calculated as a measure of total mechanical energy. The external mechanical efficiency (Eext) was assessed from stroke work and MVO2tot. Both contractile efficiency (Econ = inverse slope of the MVO2-PVA relationship) and MVO2 of the unloaded contracting heart (MVO2unl = basal MVO2 + MVO2 for excitation-contraction coupling) were calculated using pressure-volume area and MVO2tot. RESULTS: At matched heart rate (149 +/- 30 vs 147 +/- 31 min-1; mean +/- SD) and end-diastolic volume (1.3 +/- 0.2 ml), the systolic variables were significantly decreased in the stunned myocardium: aortic flow: 38 +/- 13 vs 9 +/- 11 ml.min-1, LVPmax: 112 +/- 19 vs 74 +/- 18 mmHg, and dP/dtmax: 1475 +/- 400 vs 1075 +/- 275 mmHg.s-1. Likewise, dP/dtmin was significantly impaired (-1275 +/- 250 vs -975 +/- 250). The decrease in pressure-volume area (570 +/- 280 vs 270 +/- 200 mmHg.ml.100 g-1) was not statistically significant. In contrast, both Eext (0.75 +/- 0.29 vs 0.18 +/- 0.26 arbitrary units) and Econ (31 +/- 18 vs 14 +/- 7%) were significantly decreased, whereas MVO2tot (40 +/- 9 vs 34 +/- 8 microliters.beat-1.100 g-1) and MVO2unl (26 +/- 9 vs 22 +/- 6 microliters.beat-1.100 g-1) were not. SUMMARY: Ventricular function after brief episodes of ischaemia is decreased whereas MVO2tot is maintained, i.e. external efficiency is decreased. MVO2 for the unloaded contraction remained unchanged, indicating that MVO2 for excitation-contraction coupling is inappropriately high for the depressed contractile state. The decreased contractile efficiency indicates further that O2 utilization of the contractile apparatus is disturbed during reperfusion.

Different responses of non-ischemic and post-ischemic myocardium towards Ca2+ sensitization.

We tested whether decreased Ca2+ sensitivity is a major cause for dysfunctional stunned myocardium. The experiments employed a novel Ca2+ sensitizing agent: the thiadiazinone derivative EMD 60 263. Experiments were done on 14 isolated, blood-perfused rabbit hearts. After control, seven hearts were subjected to 20 min no-flow ischemia, and then allowed to recover during 30 min reperfusion. Thereafter, EMD 60 263 was administered (3, 10 and 30 microm). For comparison, the effect of the same doses was investigated in seven non-ischemic hearts. At the low dose, the agent improved ventricular systolic function in the post-ischemic group significantly (LVPmax: 65+/-13 v 91+/-17 mmHg; dP/dtmax: 845+/-235 v 1300+/-350 mmHg/s), and non-significantly in the non-ischemic group (LVPmax: 115+/-35 v 132+/-39 mmHg; dP/dtmax: 1415+/-545 v 1885+/-720 mmHg/s). Early relaxation (dP/dtmin) was slightly improved in both groups (800+/-225 v 1050+/-220 mmHg/s post-ischemic; 1120+/-315 v 1205+/-285 mmHg/s non-ischemic). Heart rate was increased (151+/-35 v 175+/-45 beats/min) in the post-ischemic group and was unaffected in the non-ischemic group. At the higher dose, systolic ventricular function in the post-ischemic group was further improved (LVPmax: 109+/-17 mmHg, dP/dtmax: 1330+/-180 mmHg/s), but tended to decrease in the non-ischemic group (LVPmax: 121+/-40 mmHg, dP/dtmax: 1605+/-680 mmHg/s). This dose decreased heart rate in both groups (133+/-34 and 134+/-23 beats/min). 30 microm EMD 60 263 had deleterious effects in both groups. The different responses towards Ca2+ sensitization suggest that a decrease in Ca2+ sensitivity might play a role in dysfunctional stunned myocardium. Therefore, Ca2+ sensitizing agents of the thiadiazinone type could be useful to recruit a positive inotropic reserve in stunned myocardium.

Minimally invasive coronary artery bypass grafting in high-risk patients. Late follow-up with assessment of left internal mammary artery graft patency and flow by exercise transthoracic Doppler echocardiography.

UNLABELLED: Patients with significant risk factors are at increased risk of higher mortality and morbidity (9-16%) after CABG-procedures with cardiopulmonary bypass (CPB). When catheter interventions are not applicable and conventional CABG with CPB are considered to have an unacceptable perioperative risk, these patients (n=35) were scheduled for minimally invasive coronary artery bypass grafting (MIDCAB). PATIENTS AND METHODS: The risks leading to exclusion of conventional CABG procedures were: extremely impaired LV-function (EF<20%), severe pulmonary diseases, malignant carcinoma, compromised coagulation system, age >80 years with impaired physical constitution, redo-procedures after complicated initial operation, symptomatic descending thoracic aortic aneurysm, ongoing long-term intensive care treatment with unclear prognosis. All patients received the LIMA as a single graft to the LAD. One year follow-up was performed using transthoracic Doppler echocardiography at rest and during exercise. RESULTS: In 20 patients incomplete revascularization was accepted. There was no mortality, while signs for myocardial infarction were seen in two patients. Twenty-nine patients (82%) showed clear improvement of clinical symptoms, one patient needed further conventional CABG. Nine to thirteen months postoperatively (mean 10.8+/-1.6 months), there were two deaths due to noncardiac reasons. Three of the survivors (n=33) had symptoms of angina pectoris. Exercise tests revealed an improved stress tolerance (NYHA class improved from preop. III-IV to postop. I-II). The IMA graft flow increased significantly with exercise in all patients. Flow patterns in both flow velocity and volume changed to diastolic-dominant, and the ratio of diastolic to systolic time-velocity integral of >1.5 excluded a graft stenosis. CONCLUSIONS: In high-risk patients, with an increased likelihood of perioperative morbidity and mortality, the MIDCAB procedure can be performed accurately and safely. Even after incomplete revascularization of some high-risk patients, exercise tolerance was improved. Transthoracic Doppler echocardiography proved to be a clinically useful noninvasive method of assessing IMA graft function at rest and during exercise. Despite the small patient population, our late follow-up results suggest the potential benefit of MIDCAB for patients with otherwise inoperable heart disease.

Improved ventricular function by enhancing the Ca++ sensitivity in normal and stunned myocardium of isolated rabbit hearts.

A possible cause for the decreased function in postischemic reperfused (= stunned) myocardium could be a decrease in Ca++ sensitivity. To test this hypothesis, we used an agent with reportedly Ca++ sensitizing properties (EMD 57033) and performed experiments on a total of 17 isolated rabbit hearts that were perfused with an erythrocyte-containing medium in a modified Langendorff setting (hct = 30%; Ca++ = 2.0 meq/l). The hearts were divided into two groups. In one group (n = 9), the Ca++ sensitizer (30 microM) was administered to nonischemic myocardium, and in a second group (n = 8), the Ca++ sensitizer was administered after 30 min of reperfusion that followed a period of 20 min normothermic, no-flow ischemia. In the nonischemic group, addition of the agent, improved left ventricular (LV) function significantly. In the ischemic group, LV-function was depressed at 30 min reperfusion compared to control. Again, the agent improved LV-function significantly. The increase in systolic and diastolic function was comparable in both groups as well as the oxygen consumption that was significantly increased after administration of the agent. In both groups, the agent neither exhibited significant, positive chronotropic nor arrhythmogenic effects. We summarize that the novel Ca++ sensitizer acts as a potent positive inotropic agent in the isolated blood-perfused rabbit heart. Because of the agent's properties to ameliorate postischemic contractile dysfunction, this general strategy may be useful for treating poorly functioning reperfused myocardium.

Cardiac efficiency during coronary occlusion and during reperfusion after emergency revascularization under cardioprotection.

Myocardial infarction in consequence of a coronary artery occlusion presents a serious problem. It is the aim of any emergency revascularization to minimize the ischemia-induced damage or to salvage reversibly injured myocardium. In experiments on 8 anesthetized pigs, myocardial protection by orthograde perfusion with a high-volume cardioplegic solution was studied under controlled conditions. The left anterior descending artery (LAD) was occluded for 60 min. Then cardiopulmonary bypass was instituted and cardioplegia induced by 8 min perfusion of Bretschneider HTK solution into the aortic root. After 15 min global ischemia, the LAD was "revascularized' and 150 min reperfusion followed. Except for the early relaxation (dP/dtmin) and mean thickening velocity in the ischemic myocardium, all variables remained essentially unchanged during LAD occlusion. During the entire reperfusion, heart rate was significantly increased compared to control: 93 +/- 23 vs. 126 +/- 20/min. Left-ventricular (LV) peak pressure was significantly decreased at the end of the reperfusion, 104 +/- 33 and 77 +/- 22 mmHg, as was dP/dtmax:2155 +/- 655 vs. 1720 +/- 895 mmHg/s. Cardiac output was insignificantly decreased at the end of reperfusion, 2.6 +/- 0.6 vs. 2.4 +/- 0.5 L/min, whereas stroke-work index exhibited a significant deterioration: 1.2 +/- 0.6 vs. 0.5 +/- 0.3 mmHg.ml/kg. LV dP/dtmin was significantly impaired after ischemia and at the end of reperfusion, -1575 +/- 385 vs. -855 +/- 310 mmHg/s, while LV end-diastolic pressure exhibited only a moderate increase: 8 +/- 5 vs. 9 +/- 3 mmHg. MVO2, in turn, remained almost constant throughout the protocol for each of two methods by which it was predicted. The results show that global work, MVO2, and external efficiency were unchanged during early and late occlusion compared to control. During the entire reperfusion the myocardium was stunned, i.e. cardiac work was decreased at maintained MVO2. Thus, external efficiency was decreased. From these results we conclude that in reperfused myocardium after cardioplegic arrest, the oxygen is only inefficiently converted to develop force.