Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery.

BACKGROUND: Glucose-insulin-potassium (GIK) administration is advocated on the premise of preventing hyperglycaemia and hyperlipidaemia during reperfusion after cardiac interventions. Current research has focused on hyperglycaemia, largely ignoring lipids, or other substrates. The present study examines lipids and other substrates during and after on-pump coronary artery bypass grafting and how they are affected by a hyperinsulinaemic normoglycaemic clamp. METHODS: Forty-four patients were randomized to a control group (n=21) or to a GIK group (n=23) receiving a hyperinsulinaemic normoglycaemic clamp during 26 h. Plasma levels of free fatty acid (FFA), total and lipoprotein (VLDL, HDL, and LDL)-triglycerides (TG), ketone bodies, and lactate were determined. RESULTS: In the control group, mean FFA peaked at 0.76 (sem 0.05) mmol litre(-1) at early reperfusion and decreased to 0.3-0.5 mmol litre(-1) during the remaining part of the study. GIK decreased FFA levels to 0.38 (0.05) mmol litre(-1) at early reperfusion, and to low concentrations of 0.10 (0.01) mmol litre(-1) during the hyperinsulinaemic clamp. GIK reduced the area under the curve (AUC) for FFA by 75% and for TG by 53%. The reduction in total TG was reflected by a reduction in the VLDL (-54% AUC) and HDL (-42% AUC) fraction, but not in the LDL fraction. GIK prevented the increase in ketone bodies after reperfusion (-44 to -47% AUC), but was without effect on lactate levels. CONCLUSIONS: Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

Glucose-insulin therapy, plasma substrate levels and cardiac recovery after cardiac ischemic events.

INTRODUCTION: The potential usefulness of glucose-insulin therapy relies to a large extent on the premise that it prevents hyperglycemia and hyperlipidemia following cardiac ischemic events. METHODS: In this review we evaluate the literature concerning plasma glucose and free fatty acids levels during and following cardiac ischemic events. RESULTS: The data indicate that hyperlipidemia and hyperglycemia most likely occur during acute coronary ischemic syndromes in the conscious state (e.g. acute myocardial infarction) and less so during reperfusion following CABG reperfusion. This is in accordance with observations that glucose-insulin therapy during early reperfusion post CABG may actually cause hypolipidemia, because substantial hyperlipidemia does not appear to occur during that stage of cardiac surgery. DISCUSSION: Considering recent data indicating that hypolipidemia may be detrimental for cardiac function, we propose that free fatty acid levels during reperfusion post CABG with the adjunct glucose-insulin therapy need to be closely monitored. CONCLUSION: From a clinical point of view, a strategy directed at monitoring and thereafter maintaining plasma substrate levels in the normal range for both glucose (4-6 mM) and FFA (0.2-0.6 mM) as well as stimulation of glucose oxidation, promises to be the most optimal metabolic reperfusion treatment following cardiac ischemic episodes. Future (preclinical and subsequently clinical) investigations are required to investigate whether the combination of glucose-insulin therapy with concomitant lipid administration may be beneficial in the setting of reperfusion post CABG.

Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during coronary artery surgery.

BACKGROUND: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG. METHODS: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1)) normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD). RESULTS: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group. CONCLUSION: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.

Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery.

BACKGROUND: The clinical benefits of glucose-insulin-potassium (GIK) and tight glycaemic control in patients undergoing coronary artery bypass grafting (CABG) may be partly explained by an anti-inflammatory effect. We applied GIK as a hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on systemic inflammation in patients undergoing CABG. METHODS: Data obtained in 21 non-diabetic patients with normal left ventricular function scheduled for elective coronary artery surgery, who were randomly allocated to a control or GIK group, were analysed. In GIK patients, regular insulin was infused at a fixed rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1). Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and serum amyloid A (SAA) were measured on the day of surgery and on the first and second postoperative days (POD1 and POD2). RESULTS: In the GIK group hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control patients, hyperglycaemia developed in >80% of all measurements in the presence of low endogenous insulin levels. CRP and SAA levels increased in both groups, with maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA levels. Interleukin levels increased significantly in both groups following cardiopulmonary bypass, but no differences were found between the groups. CONCLUSION: Hyperinsulinaemic normoglycaemic clamp is an effective method of maintaining tight glycaemic control in patients undergoing CABG and it attenuates the systemic inflammatory response in these patients. This effect may partly contribute to the reported beneficial effect of glycaemic control in patients undergoing CABG.

[Experiences of relatives of donors with the donation procedure; comparison between 1995 and 1998]. / Ervaringen van nabestaanden van donoren met de donatieprocedure; vergelijking tussen 1995 en 1998.

OBJECTIVE: To determine the experience of the relatives of organ and tissue donors, immediately before, during and soon after the donation procedure. DESIGN: Questionnaire. METHOD: At two national one-day meetings at which about 10% of the families of donors between 1991 and 1998 were represented, the participants completed a questionnaire with questions about their appreciation of the communication with the different health care professionals. The appreciation was scored on a 7-point scale. RESULTS: Most relatives looked back with satisfaction on the events in the hospital and soon thereafter; the appreciation was 'a little satisfied' to 'satisfied'. The relatives in non-heart-beating kidney transplantation were more satisfied compared to those confronted with the brain death transplantation, with regard to the conversation in which the death was announced as well as to the conversation regarding the donation procedure. Relatives in 1998 were more positive about some specific aspects than in 1995, notably concerning explanation of the phenomenon of brain death. Satisfaction was primarily influenced by the way in which the news of death was conveyed and the aftercare by the transplant coordinator. The moment donation was addressed and the moment the relatives said 'good-bye' to their beloved were the next important factors.

Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: assessment by intravenous administration of nitroglycerin.

We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.

A critical appraisal of the rate pressure product as index of myocardial oxygen consumption for the study of metabolic coronary flow regulation.

For the assessment of metabolic coronary vasodilatation, changes in systolic rate pressure product (RPP) are frequently used to estimate the pacing- or exercise induced changes in myocardial oxygen consumption (MVO2). The present study was designed to test whether this is justified in patients with coronary artery disease. To study the relation between RPP and changes in MVO2 under different conditions, we used data from 21 patients who participated in two previous studies investigating the effect of nitroglycerin (NTG) and anaesthesia on metabolic coronary flow regulation. At control, during administration of NTG 1 microg/kg/min (n=11), and during anaesthesia (n=10), coronary sinus blood flow, MVO2 and RPP were measured at sinus rhythm and during atrial pacing (30 bpm above sinus rate) and the relation between the percentage increase in RPP (delta%RPP) and MVO2 delta%MVO2) was analysed, using standard linear regression analysis. Although a significant relation between delta%MVO2 and delta%RPP was found at control and during anaesthesia, prediction intervals were very wide and only 40% and 60% of the variation in delta%MVO2, respectively, could be explained by the variation in delta%RPP. During administration of NTG 1 microg/kg/min no significant relation was found between delta%MVO2 and delta%RPP. Thus, for the study of metabolic coronary flow regulation, pacing induced changes in MVO2 cannot be predicted accurately from changes in RPP.

The effect of nitroglycerin on pacing-induced changes in myocardial oxygen consumption and metabolic coronary vasodilation in patients with coronary artery disease.

UNLABELLED: In the present study, we assessed the potential effect of nitroglycerin IV (NTG), a donor of exogenous nitric oxide, on metabolic coronary flow control in patients with coronary artery disease. In 12 patients scheduled for coronary artery surgery, arterial blood pressure, pulmonary capillary wedge pressure, coronary sinus blood flow (continuous thermodilution), myocardial oxygen supply (DVO2), and myocardial oxygen consumption (MVO2) were measured at sinus rhythm and in response to atrial pacing at 30 bpm greater than baseline sinus rate. These measurements were repeated during infusion of NTG 1 and 2 microg x kg(-1) x min(-1). At control, in the absence of NTG, MVO2 increased from 13.7 +/- 3.4 mL O2/min during sinus rhythm to 19.3 +/- 5.5 mL O2/min during pacing. NTG 1 and 2 microg x kg(-1) x min(-1) blunted the pacing-induced increase in MVO2 dose-dependently. During NTG 1 microg x kg(-1) x min(-1), MVO2 increased from 12.9 +/- 3.3 mL O2/min at sinus rhythm to 17.3 +/- 4.7 mL O2/min during pacing (P = 0.01 versus control pacing); during NTG 2 microg x kg(-1) x min(-1), MVO2 increased from 13.4 +/- 3.3 mL O2/min to 15.9 +/- 3.7 mL O2/min (P = 0.008 versus control pacing). However, the pacing-induced increase in DVO2 per mL O2/min increase in MVO2 (delta DVO2/delta MVO2), was significantly greater during the infusion of NTG 2 microg x kg(-1) x min(-1) (1.85 +/- 0.56; P = 0.023) compared with control (1.51 +/- 0.22). This was associated with an increase in coronary sinus hemoglobin oxygen saturation (30% +/- 5% at control pacing and 34% +/- 6% during pacing with NTG 2 microg x kg(-1) x min(-1); P = 0.018), which indicates that during the infusion of NTG, there was more metabolic coronary vasodilation than achievable solely on the basis of the metabolic stimulus. IMPLICATIONS: Our findings suggest that nitroglycerin, a donor of exogenous nitric oxide, reduces pacing-induced increases in myocardial oxygen consumption and enhances metabolic coronary vasodilation in patients with coronary artery disease, in whom endogenous nitric oxide activity may be reduced.

Chronic cardiac denervation affects the speed of coronary vascular regulation.

OBJECTIVE: We tested the hypothesis that the rate of adaptation of coronary metabolic vasodilatation and autoregulation is modulated by the cardiac nerves. METHODS: Anaesthetised dogs (seven innervated (control) and seven with denervated hearts) were subjected to controlled pressure perfusion of the left main coronary artery. Heart rate was controlled by pacing. RESULTS: The steady state autoregulation curves and metabolic regulation curves were similar in the two groups. A sudden increase or decrease in heart rate was associated with a faster response (22% shorter half-times) in the innervated than the denervated dogs (P < 0.001). A sudden increase or decrease in coronary arterial perfusion pressure was associated with a slower response (24% longer half-times) in the innervated than the denervated hearts (P < 0.005). CONCLUSIONS: We conclude that the speed of response to metabolic and perfusion pressure changes is partly mediated by cardio-cardiac reflexes. Reflex coronary vasodilatation appears to reinforce the metabolic vasodilatation of a heart rate increase and oppose the vasoconstriction in response to increased perfusion pressure.

Intracoronary-administered urapidil does not influence myocardial contractility, metabolic activity, or coronary sinus blood flow in humans.

OBJECTIVE: To compare the acute effect of intracoronary administration of urapidil and saline on myocardial contractility and metabolic activity. DESIGN: Prospective, controlled, open-label study. SETTING: University teaching hospital. PARTICIPANTS AND INTERVENTIONS: Eight patients with stable coronary artery disease (CAD) undergoing elective percutaneous transluminal coronary angioplasty (PTCA) received normal saline followed by urapidil, 4 mg, injected directly into the left main coronary artery. MEASUREMENTS AND MAIN RESULTS: Because local intracoronary administration is a non-steady-state condition, an in vitro model was used before the clinical experiments to establish the kinetic effects of acute administration of urapidil. The clinical experiments were performed in eight patients with CAD after PTCA. Measurements included a complete hemodynamic profile, coronary sinus blood flow (continuous thermodilution), left ventricular (LV) peak (+) dP/dt, LV peak (-) dP/dt, LV dP/dt/P(D)40, and LV end-diastolic pressures. Arterial and coronary venous blood samples were also obtained for the calculation of myocardial oxygen consumption. Baseline measurements I were first obtained, followed by intracoronary injection of 2 mL of saline. Additional measurements were obtained 1, 5, and 10 minutes after administration of saline. After a resting period (15 minutes), baseline measurements II, and intracoronary injection of urapidil, 4 mg (dissolved in 2 mL saline), additional measurements were obtained 1, 5, and 10 minutes later. Heart rate decreased 2.7+/-3.5 beats/min after injection of saline, whereas heart rate increased 2.0+/-1.8 beats/min after intracoronary urapidil, resulting in a significant difference in treatment effect (p = 0.003). There were no additional differences in treatment effect for any of the other measured or calculated parameters reflecting systemic hemodynamics, LV contractility, coronary dynamics, and myocardial metabolic activity. CONCLUSION: The results suggest that intracoronary bolus administration of preservative-free urapidil, 4 mg, is not associated with any detectable effect on myocardial contractility or coronary smooth muscle in awake nonsurgical patients with CAD, after PTCA.

Cardiovascular responses, arterial oxygen saturation and plasma catecholamine concentration during upper gastrointestinal endoscopy using conscious sedation with midazolam or propofol.

Hypoventilation as a consequence of deep intravenous sedation is the most frequently reported cause of cardiac arrest during upper gastrointestinal endoscopy (UGIE). Haemodynamic stress can contribute to myocardial ischaemia; therefore, this study was designed to observe prospectively the cardiorespiratory changes during UGIE using either midazolam or propofol for conscious sedation. Thirty-four patients, aged 50 years and older, ASA physical status I-III, scheduled for elective UGIE with sedation, were studied. Oxygen saturation, heart rate, non-invasive blood pressure and Holter ECG were recorded continuously starting 15 min before sedation until 15 min after the endoscopy. In addition, plasma catecholamine concentrations were determined. The results of this study are consistent with previous reports that cardiopulmonary events may occur during endoscopy, with or without sedation. Both midazolam and propofol sedation may provide some protection against haemodynamic stress in response to insertion and manipulation of the endoscope, but sedation can also contribute to the occurrence of hypoxaemia.

[Continuous pressure is preferred to flow triggering of respiration in the apnea test following the protocol for brain death determination]. / Liever druk-dan flowgestuurde beademing bij de apneutest volgens het hersendoodprotocol.

The apnea test is part of the brain death protocol of the National Health Council. If the patient is being given positive end-pressure respiration, he must not be uncoupled from the respirator. The apnea test should then be done by means of continuous positive airway pressure. Pressure triggering rather than the extremely sensitive flow triggering should then be chosen to trigger the respiration, since otherwise the patient may unjustifiably be declared 'not brain dead' as a result of slight aspecific movements (bumping against the bed, beating of the heart).

[The regional explantation team: an important contribution to organ procurement for transplantation in the Netherlands]. / Het regionale explantatieteam: een belangrijke bijdrage aan orgaanverwerving voor transplantatie in Nederland.

If organ donations concern not only the kidneys, but also the liver, pancreas and, sometimes, the heart and (or) lungs, several surgical removal teams, often from different (foreign) transplantation centres, may be involved. This has created organizatory problems resulting in loss of organs for transplantation. In the Nijmegen area since October 1994 a removal team has been active that in the regional donor hospital removes all abdominal organs from the donor on behalf of the various transplantation centres. This regional removal team performed 105 multi-organ explanations in the period from October 1994 to December 1997. The reports that came back from the transplantation centres that had received the organs showed that none of these organs had been lost for transplantation through organizatory problems or anatomical damage. Experiences of operating room staff involved were positive: it was especially the standard surgical techniques and the quiet in the operating room that were appreciated. Special removal teams may greatly improve the evolution of organ donation in the Netherlands.

[Kidney donation by a 'non-heart-beating' donor from an ethical perspective]. / Nierdonatie door een 'hartdode donor' ('non-heartbeating donor') in ethisch perspectief.

In asystolic patients, kidney donation is possible by using a non-heart-beating (NHB) donation procedure. This involves in situ perfusion of the kidneys by inserting a catheter into the femoral artery and flushing cold fluid through the kidneys. The introduction of an NHB donation programme leads to ethical questions concerning the guarantees for prudent procedure: How should death of a patient be defined in case of NHB donation? Is there a strict separation of responsibilities of the medical teams in the different phases of the procedure (patient treatment and actual donation procedure)? Are sufficient attention and care given to the relatives? Does the NHB donation procedure not interfere with the care of a patient who is expected to die soon? Extensive discussion with the Medical Ethics Committee of the University Hospital Nijmegen, the Netherlands, has led to a protocol for NHB kidney donation that meets the required guarantees.

A randomized multicenter double-blind comparison of urapidil and ketanserin in hypertensive patients after coronary artery surgery.

OBJECTIVES: To compare the hemodynamic responses, safety, and efficacy of urapidil and ketanserin in hypertensive patients after coronary artery surgery. DESIGN: Randomized double-blind study. SETTING: Multi-institutional. PARTICIPANTS: One hundred twenty-two patients undergoing elective coronary artery surgery. INTERVENTIONS: When hypertension (defined as mean arterial pressure > 85 mmHg) developed within the first 2 hours after arrival in the intensive care unit, patients received urapidil (n = 62) or ketanserin (n = 60) to reach a mean arterial pressure between 65 and 75 mmHg. Urapidil was administered by repeated bolus injections (25 to 125 mg) followed by a continuous infusion of maximally 50 micrograms/kg/min. Ketanserin was administered by repeated bolus injections (10 to 50 mg) followed by a continuous infusion of maximally 4.0 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was determined at baseline and at 30 and 60 minutes after start of study medication. In the urapidil group, mean arterial pressure (+/-SD) decreased significantly from 100.6 +/- 12.4 mmHg at baseline to 74.6 +/- 12.1 mmHg at 30 minutes and 73.5 +/- 13.8 mmHg at 60 minutes. In the ketanserin group, mean arterial pressure decreased significantly from 98.7 +/- 10.7 mmHg at baseline to 83.5 +/- 16.8 mmHg at 30 minutes and 83.1 +/- 15.3 mmHg at 60 minutes. Between the groups, there was a significant difference in the degree of lowering mean arterial pressure at 30 and 60 minutes. Heart rate increased significantly by 5.8 +/- 12.7 (30 minutes) and 8.6 +/- 16.5 (60 minutes) beats/min in the ketanserin group. In the urapidil group, no changes in heart rate occurred. Cardiac output increased to the same extent (0.7 L/min) in both groups. Within and between the groups, there were no relevant changes in pulmonary filling pressures. The number of patients not responding adequately to the study medication (mean arterial pressure > 85 mmHg after 30 minutes despite the maximum doses of study medication) was comparable in both groups (9 [U] v 13 [K]). Adverse events attributable to the study medication occurred to a similar degree in both groups. In the patients treated with urapidil, a significantly higher incidence (32.3%) of hypotension (mean arterial pressure < or = 65 mmHg for more than 10 minutes) occurred after 60 minutes of continuous infusion. CONCLUSIONS: In contrast to ketanserin, urapidil did not increase heart rate. Urapidil was more effective in lowering arterial blood pressure than ketanserin. However, one third of the patients treated with urapidil developed hypotension after 60 minutes of continuous infusion.

Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans.

OBJECTIVE: Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major determinant of coronary blood flow; therefore, the true vasodilating properties of coronary vasodilating drugs that may have an effect on oxygen consumption cannot be correctly assessed from blood flow changes alone. DESIGN: Prospective, controlled trial. SETTING: Academic hospital. PATIENTS: 12 patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass grafting. INTERVENTIONS: Cardiac pacing at 30 beats/min above sinus rhythm in awake and anaesthetised patients (fentanyl/pancuronium bromide). MAIN OUTCOME MEASURES: Myocardial oxygen supply, defined as coronary sinus blood flow multiplied by arterial oxygen content; myocardial oxygen demand, defined as coronary sinus blood flow multiplied by arteriovenous oxygen content difference. The change in oxygen demand induced by pacing was related to the change in myocardial oxygen supply in awake and anaesthetised patients. This myocardial oxygen supply:demand ratio determined in the reference study was compared with that induced by intravenous and intracoronary drugs (nifedipine, felodipine, urapidil, and sodium nitroprusside) in two pharmacological studies: patients with CAD undergoing cardiac surgery (45 treated with sodium nitroprusside, 27 with nifedipine, and 27 with urapidil to manage arterial blood pressure); and patients with unstable angina (and a similar degree of CAD) undergoing cardiac catheterisation for diagnostic purposes (10 treated with intracoronary nifedipine and 10 with intracoronary felodipine). RESULTS: When awake, the ratio of pacing induced oxygen supply:demand changes in the 12 reference study patients was 1.50 (95% confidence intervals (CI), 1.41-1.58), similar to the 1.45 (1.35-1.56) measured in the same patients after induction of anaesthesia. Anaesthesia per se did not increase coronary oxygen supply above the expected increase related to demand changes. The only significant change in the oxygen supply:demand ratio was induced by intracoronary bolus administration of nifedipine and felodipine (10.6 (SE 1.9) and 13.9 (1.9) ml/min, respectively, above the demand related supply). CONCLUSIONS: Quantification of coronary vasoactive properties in relation to the physiological reference ratio between myocardial oxygen supply and demand may be a powerful tool to differentiate between true and apparent coronary vasoactive drugs.

Effects of dobutamine and enoximone on transmitral and pulmonary venous flow characteristics in patients with left ventricular dysfunction after coronary artery bypass grafting.

OBJECTIVES: To assess the effects of dobutamine and enoximone on transmitral (TMF) and pulmonary venous flow (PVF) characteristics. DESIGN: Prospective and randomized. SETTING: A university hospital intensive care unit. PARTICIPANTS: Thirty patients with moderate left ventricular dysfunction after coronary artery bypass grafting (CABG). INTERVENTIONS: Patients received either dobutamine, 10 micrograms/kg/min, or enoximone, 20 micrograms/kg/min, for the treatment of a low cardiac index (CI) (< 2.2 L/min/m2). MEASUREMENTS AND MAIN RESULTS: Both drugs significantly (p < 0.05) increased CI from 1.91 +/- 0.17 (dobutamine) and 1.97 +/- 0.17 (enoximone) at baseline to 2.86 +/- 0.70 and 2.84 +/- 0.39 L/min/m2, respectively. Compared with the enoximone (enox)-treated group, the administration of dobutamine (dob) resulted in significantly (p < 0.05) greater increases in mean arterial pressure (dob: 18 +/- 9% v enox: -2 +/- 7%), heart rate (dob: 24 +/- 13% v enox: 3 +/- 5%) and pulmonary artery pressure (dob: 5 +/- 10% v enox: -4 +/- 9%). In contrast, the increase in stroke volume index was significantly less in the dobutamine-treated group (dob: 22 +/- 27% v enox: 41 +/- 21%). The TMF indices, peak E, and peak A wave increased significantly (p < 0.05) after both dobutamine (baseline: 37.3 +/- 6.7 and 41.1 +/- 9.3; max dose: 42.4 +/- 4.3 and 49.0 +/- 10.2 cm/s) and enoximone (baseline: 36.2 +/- 7.5 and 44.2 +/- 10.9; max dose: 40.5 +/- 5.0 and 49.4 +/- 12.1 cm/s) without significantly altering the E/A ratio. Only dobutamine significantly (p < 0.05) decreased isovolumic relaxation time from 109 +/- 24 to 94 +/- 21 ms. There was no significant change in isovolumic relaxation time between the dobutamine (-12% +/- 17%)- and the enoximone (-4% +/- 21%)- treated group. PVF recordings demonstrated a significant increase in time velocity integrals of the S wave with both dobutamine (12.2 +/- 3.1 v 13.7 +/- 3.2 cm) and enoximone (11.0 +/- 3.0 v 12.2 +/- 3.2 cm). No changes in the systolic fraction of the PVF were noted. CONCLUSIONS: There were no major differences in parameters reflecting diastolic function between the dobutamine- and the enoximone-treated groups.

Myocardial stunning, hibernation, and ischemic preconditioning.

From the present review, it may be concluded that myocardial ischemia results in far more complicated syndromes than previously realized. Although not all aspects of the issues discussed in this review are currently a clinical reality in the daily practice of cardiovascular anesthesiologists, the understanding and application of these concepts are growing rapidly. Indications for revascularization procedures will be adjusted in patients with evidence of hibernating myocardium. In the future, postoperative myocardial dysfunction may be diminished by the prevention of myocardial stunning, for instance by altering the composition of the cardioplegic solution and other interventions. Finally, additional advances may involve reduction of the extent of perioperative myocardial infarctions by application of ischemic preconditioning.