Hans Joachim Geissler

Impact of cardiopulmonary bypass management on postcardiac surgery renal function.

Objective: Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction and up to 4% of patients with normal preoperative renal function develop acute renal failure (ARF) requiring dialysis. According to recent investigations, CPB management is not evidence-based and, thus, current clinical CPB practice may favor renal dysfunction. The purpose of our study was to investigate if postcardiac surgery renal dysfunction is influenced by CPB management. Methods: We selected three groups of patients with normal preoperative renal function who had been subjected to cardiac surgical procedures on CPB: 44 patients with postoperative ARF requiring hemofiltration/dialysis (ARF group), 51 patients with postoperative renal dysfunction not requiring hemofiltration/dialysis (serum creatinine increase > 0.5 mg/dl within 48 h postsurgery: CREAgroup), and 48 patients with normal postoperative renal function (Control group). The patients’ on-line CPB records were analyzed for CPB duration, CPB perfusion pressure, CPB flow, and periods on CPB at a perfusion pressure < 60 mmHg. On-CPB diuretic and vasoconstrictor medication was recorded. Results: Patient demographics were similar for the three groups. In the ARF group, CPB duration was longer (166± 77 [standard deviation, SD] min) compared to CREA (115± 41 min; p < 0.001) and to Control groups (107± 40 min; p < 0.001), and mean CPB flow was lower (2.35± 0.36 l/min/m2) compared to CREA (2.61± 0.35 l/min/m2; p=0.0015) and to Control groups (2.51± 0.33 l/min/m2; p = 0.09). Mean arterial pressure on CPB (ARF: 61± 10; CREA: 60± 7; Control: 63± 9 mmHg; p = 0.19) as well as furosemide and norepinephrine medication on CPB were similar for the groups. Compared to Control (46± 26 min), CPB duration at arterial pressures < 60 mmHg was longer in ARF (78± 60 min; p = 0.034) and in CREA (62± 36 min; p=0.048). Conclusions: Our data suggest that current clinical CPB management impacts postoperative renal function. We found that patients with normal preoperative renal function who developed postoperative ARF had longer CPB duration, lower CPB perfusion flow, and longer periods on CPB at pressures < 60 mmHg compared to patients with no post CPB ARF. However, our data do not allow us to separate these CPB-related factors from the potential influence of perioperative low cardiac output syndrome as a cause for postoperative ARF. Thus, future clinical studies are required to elucidate CPB-induced ARF and to optimize CPB management for ARF prevention.

Effect of body repositioning after venous air embolism. An echocardiographic study

Background Current therapy for massive venous air embolism (VAE) may include the use of the left lateral recumbent (LLR) position, although its effectiveness has been questioned. This study used transesophageal echocardiography to evaluate the effect of body repositioning on intracardiac air and acute cardiac dimension changes. Methods Eighteen anesthetized dogs in the supine position received a venous air injection of 2.5 ml/kg at a rate of 5 ml/s. After 1 min the dogs were repositioned into either the LLR, LLR 10 degrees head down (LLR‐10 degrees), right lateral recumbence, or remained in the supine position. Results Repositioning after VAE resulted in relocation of intracardiac air to nondependent areas of the right heart. Peak right ventricular (RV) diameter increase and mean arterial pressure decrease were greater in the repositioned animals compared with those in the supine position (P < 0.05). Right ventricular diameter and mean arterial pressure showed an inverse correlation (r = 0.81). Peak left atrial diameter decrease was greater in the LLR and LLR‐10 degrees positions compared with the supine position (P < 0.05). Repositioning did not influence peak pulmonary artery pressure increase, and no correlation was found between RV diameter and pulmonary artery pressure. All animals showed electrocardiogram and echocardiographic changes reconcilable with myocardial ischemia. Conclusions In dogs, body repositioning after VAE provided no benefit in hemodynamic performance or cardiac dimension changes, although relocation of intracardiac air was demonstrated. Right ventricular air did not appear to result in significant RV outflow obstruction, as pulmonary artery pressure increased uniformly in all groups and was not influenced by the relocation of intracardiac air. The combination of increased RV afterload and arterial hypotension, possibly with subsequent RV ischemia rather than RV outflow obstruction by an airlock appeared to be the primary mechanism for cardiac dysfunction after VAE.

Myocardial β-Blockade as an Alternative to Cardioplegic Arrest during Coronary Artery Surgery

Abstract The authors recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm s-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting s-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a−csDLAC). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6±0.8 grafts during 64±20xa0min cross-clamp time (s-blocker: 3.5±0.9 grafts during 68±22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a−csDLAC −1.0±0.6 versus −0.1±0.2 mmol/litre in s-blocker hearts; P

Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction

UNLABELLEDnOur recent work demonstrated that normothermic continuous antegrade blood cardioplegia results in cardiac dysfunction related to myocardial oedema. This oedema was partially due to increased myocardial microvascular fluid filtration induced by crystalloid hemodilution. We hypothesized that increasing the colloid osmotic pressure of blood cardioplegia would stop fluid filtration into the cardiac interstitium, thus preventing myocardial oedema and cardiac dysfunction.nnnMETHODSnWe determined myocardial water content in six dogs by microgravimetry and myocardial lymph flow from the major prenodal cardiac lymphatic. Preload recruitable stroke work was derived from sonomicrometry and micromanometry. The dogs were subjected to normothermic cardiopulmonary bypass primed with 6% hetastarch and 1 h of normothermic continuous antegrade blood cardioplegia (4:1 blood:6% hetastarch colloid osmotic pressure 21 +/- 2 mmHg) delivered at 50 mmHg perfusion pressure.nnnRESULTSnWe found that despite increased colloid osmotic pressure, a small but significant increase in myocardial water content still occurred during blood cardioplegia. As myocardial lymph flow virtually ceased during cardioplegia, myocardial microvascular filtration must have been present. However, increased myocardial lymph flow following cardioplegia resulted in complete oedema resolution associated with normal left ventricular performance post-cardiopulmonary bypass.nnnCONCLUSIONSnOur data show that the plegic myocardium is prone to oedema formation because of both relatively enhanced fluid filtration and lymph flow cessation. We conclude that increasing the colloid osmotic pressure of normothermic blood cardioplegia minimizes myocardial oedema, thus preventing post-cardiopulmonary bypass cardiac dysfunction.

Lymph Angiogenesis After Lung Transplantation and Relation to Acute Organ Rejection in Humans

BACKGROUNDnAcute rejection after kidney transplantation was found to be associated with increased recipient-derived lymph angiogenesis. However, the relation of lymph angiogenesis to acute rejection in lung transplantation has not yet been investigated.nnnMETHODSnTransbronchial biopsies from 23 lung transplant recipients (47 + or - 15 years old, 15 male, 19 double lungs, 4 single lungs), taken at 14 and 90 days after transplantation were investigated. Immunohistostaining for PROX-1 (an lymphatic endothelial marker) and for vascular endothelial growth factor receptor (VEGFR) 1 and 2 (blood capillary markers) was performed. Biopsies with no sign of rejection (International Society for Heart and Lung Transplantation [ISHLT] grade A0, n = 27) were compared with biopsies with rejection grade A1/A2 (n = 19).nnnRESULTSnBiopsies with ISHLT rejection grade A1 or A2 showed a significantly higher density of PROX-1 marked lymphatics in comparison with biopsies of grade A0 at 14 days (p < 0.001) and at 90 days (p < 0.001) after transplantation, and in the collective comparison (all biopsies with ISHLT grade A1 or A2 versus all biopsies with grade A0, p < 0.001). For VEGFR-1 and VEGFR-2, no difference was found between ISHLT grade A1 or A2 compared with grade A0, neither at 14 or 90 days nor in the collective comparison.nnnCONCLUSIONSnIncreased lymphatic angiogenesis after lung transplantation, demonstrated by increased density of the PROX-1 lymphatic endothelial marker, was associated with histologically evident acute organ rejection in humans. Although the exact role of lymphatic angiogenesis in acute organ rejection remains to be determined, further study of the interaction between the microvasculature and acute rejection seems warranted. Pending further investigation, analysis of PROX-1 density may develop into a new tool for rejection monitoring, supplementing conventional rejection grading.

Augmenting cardiac contractility hastens myocardial edema resolution after cardiopulmonary bypass and cardioplegic arrest

Although myocardial edema is associated with cardio-pulmonary bypass (CPB) and cardioplegic arrest (CPA), interventions to expedite edema removal have not been investigated. The primary mechanism for the removal of excess interstitial fluid in the heart is myocardial lymphatic drainage, but lymphatic function can be impaired by decreased contractility because of edema. The purpose of this study was to determine whether enhancing cardiac contractility would increase myocardial lymphatic function and hasten edema resolution after CPB. Sixteen dogs were subjected to CPB and 1 h of hypothermic CPA. After weaning from CPB, 10 dogs received an intravenous dobutamine infusion and 6 dogs received no inotropic support. We determined myocardial lymph driving pressure from the major cardiac lymphatic, myocardial water content by using microgravimetry, and the peak rate of left ventricular pressure increase (dP/dtmax) by using micromanometry. Measurements were taken at baseline, during CPA, and 60 min after CPB. Compared with controls, dobutamine-treated dogs had an increased dP/dtmax (P < 0.05), which was associated with higher lymph driving pressures (P < 0.05), resulting in lower myocardial water gain 1 h after CPB (P < 0.05). We conclude that the resolution of myocardial edema after CPB was hastened by dobutamine. Organized ventricular contraction and myocardial contractility seem to be important determinants of myocardial lymphatic function and myocardial edema removal. These findings suggest that the administration of inotropic drugs after CPB may hasten cardiac recovery. Implications: Myocardial edema, which develops during cardiopulmonary bypass and cardioplegic arrest, contributes to cardiac dysfunction after heart surgery. This study demonstrated that enhancement of cardiac contractility by the administration of dobutamine after cardiopulmonary bypass and cardioplegic arrest was associated with increased myocardial lymphatic function and hastened edema resolution in dogs. (Anesth Analg 1997;85:987-92)

Cooling Gradients and Formation of Gaseous Microemboli With Cardiopulmonary Bypass: An Echocardiographic Study

BACKGROUNDnPrevious studies demonstrated gas emboli formation during rewarming from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded a critical threshold. It also has been suggested that formation of arterial gas emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patients blood. The purpose of this study was to determine under what circumstances gas emboli formation would occur during cooling on cardio-pulmonary bypass.nnnMETHODSnEight anesthetized mongreal dogs were placed on cardiopulmonary bypass using a roller pump, membrane oxygenator, and arterial line filter. For emboli detection, we positioned a transesophageal echocardiographic probe at the aortic arch distal to the aortic cannula and Doppler probes at the common carotid artery and the arterial line. Cooling gradients between normothermic blood and cooled arterial perfusate of 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 0 degree C (isothermal controls) were investigated. In addition to preestablished temperature gradients, we investigated the effect of rapid cooling (maximal flow through the heat exchanger at a water bath temperature of 4 degrees C) after the initiation of normothermic cardiopulmonary bypass.nnnRESULTSnMinimal gas emboli were detected at the aortic arch at gradients of 10 degrees C or greater. The incidence of emboli was related directly to the magnitude of the temperature gradient (p < 0.01). No emboli were detected at the carotid artery. During rapid cooling, no emboli were observed either at the aorta or at the carotid artery.nnnCONCLUSIONSnCooling gradients of 10 degrees C or greater may be associated with gas emboli formation, but they may be of limited clinical significance because no emboli were detected distal to the aortic arch. During the application of rapid cooling, no emboli formation was observed.

Myocardial protection with high-dose β-blockade in acute myocardial ischemia

Objective: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose b-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose b-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. Methods: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose b-blockade during continuous coronary perfusion (ESMO, na 6) or antegrade continuous warm blood cardioplegia (WBC, na 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. Results: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 ^ 0.49 vs. 0.76 ^ 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 ^ 0.19 and 1.13 ^ 0.32% vs. 0.07 ^ 0.25 and 0.04 ^ 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 ^ 6 and 94.7 ^ 4.6% of baseline vs. 85.3 ^ 4.9 and 74.7 ^ 7.6% of baseline). However, regional LV function showed no significant difference between groups. Conclusions: High-dose b-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose bblockade may be an applicable alternative to cardioplegic arrest. q 2000 Elsevier Science B.V. All rights reserved.

Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs

BACKGROUNDnInfarct size can be reduced by beta-blockade in acute myocardial ischemia. However it is unknown whether myocardial salvage is still effective when beta-blockade is limited to reperfusion.nnnMETHODSnAfter initiation of cardiopulmonary bypass, 20 dogs were submitted to 2 hours of regional left ventricular ischemia, followed by 2 hours of reperfusion. In 11 dogs beta-blockade was started with the onset of reperfusion (esmolol group). The remaining dogs received no treatment (control, n = 9). Infarct size was determined by tetrazolium chloride staining. Myocardial water content (MWC) and ultrastructural damage (electronmicroscopy) were determined from transmural biopsies.nnnRESULTSnInfarct size was significantly smaller in the esmolol group compared with control (49% versus 68%, p < 0.05). After 2 hours ischemia there was no difference in MWC between groups, whereas after 2 hours reperfusion MWC of ischemic myocardium was significantly lower in the esmolol group than in the control (p < 0.05). Ultrastructural changes were typical for ischemia-reperfusion injury in both groups.nnnCONCLUSIONSnBeta-blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion.

β-blockade as an alternative to cardioplegic arrest during cardiopulmonary bypass

Abstract Background . As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using β-blocker–induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. Methods . Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry. Results . Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest ( p p Conclusions . In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses β-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.