Biomarkers of inflammation in major vascular surgery: a prospective randomised trial.

BACKGROUND: Surgery induces inflammation and pro-inflammatory cytokines are associated with post-operative complications. In cardiac surgery, it has been shown that volatile anaesthetics have cardioprotective properties. We explored whether sevoflurane affects the pro-inflammatory response favourably compared with total intravenous anaesthesia (TIVA) after surgery. METHODS: We measured monocyte chemotactic protein 1 (MCP-1), matrix metalloproteinase 9 (MMP-9), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), interleukin (IL)-6 and IL-8 perioperatively and evaluated if the anaesthetic regimen affected these mediators. Our hypothesis was that sevoflurane-based anaesthesia is associated with a reduced release of biomarkers of inflammation compared with TIVA with propofol/remifentanil. RESULTS: In the total population, MCP-1, MMP-9, IL-6 and IL-8 increased 30 min after arrival intensive care unit, compared with before surgery (P < 0.001), whereas CRP and VCAM-1 transiently declined (P < 0.001). From 30 min after arrival intensive care unit to 1st post-operative day, MCP-1 and IL-6 levels declined (P < 0.001), CRP and VCAM-1 increased (P < 0.001), whereas MMP-9 and IL-8 were not significantly altered. Pre-operatively there were no significant differences in any variables between the two anaesthetic groups. Lower levels of MCP-1 and IL-8 (P < 0.001) and higher levels of IL-6 and MMP-9 (P = 0.003) were found in the sevoflurane group, compared with the TIVA group 30 min post-operatively. CRP and VCAM-1 levels did not differ. There were no significant differences between the two anaesthetic groups before surgery or at 1st post-operative day. CONCLUSION: We found an inflammatory response during the observation period, which was modified by the anaesthetic regimen in the early phase. This short-lasting difference is probably too short to support a cardioprotective effect of sevoflurane compared with TIVA in open abdominal aortic surgery.

Dynamic variables and fluid responsiveness in patients for aortic stenosis surgery.

BACKGROUND: Aortic stenosis is the most common valvular disease in developed countries, but it carries an increased mortality during non-cardiac surgery underscoring the importance of adequate hemodynamic management. Further, haemodynamic management of patients immediately after surgery for aortic stenosis can be challenging. Prediction of fluid responsiveness using dynamic variables has not been sufficiently studied in patients for aortic stenosis surgery. METHODS: Observational study evaluating fluid responsiveness on 32 (31 analysed) patients scheduled for aortic valve replacement due to aortic stenosis on mechanical ventilation before and after valve replacement. Increase in stroke volume (oesophagus Doppler) ≥ 15% to a fluid challenge defined fluid responders. RESULTS: Before surgery (31 fluid loads performed in 31 patients), areas under receiver operating characteristics curves (95% confidence intervals) were stroke volume variation (from arterial pulse contour analysis) 0.77 (0.58-0.90), pulse pressure variation 0.75 (0.54-0.90) and Pleth variability index 0.51 (0.31-0.69). After aortic valve replacement (31 fluid loads performed in 23 patients) the values were stroke volume variation 0.90 (0.74-0.98), pulse pressure variation 0.95 (0.80-1.0) and Pleth variability index 0.72 (0.52-0.87). CONCLUSIONS: The arterial pressure-based variables had moderate predictive values before valve replacement, but it predicted fluid responsiveness well postoperatively. Pleth variability index did not predict fluid responsiveness preoperatively, and it had a moderate predictive value postoperatively. These results indicate that arterial pressure-based dynamic variables have limited potential to guide fluid therapy in patients with aortic stenosis. Their ability to guide fluid therapy after aortic valve replacement seems better.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia.

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified.

Dynamic variables of fluid responsiveness during pneumoperitoneum and laparoscopic surgery.

BACKGROUND: Few data exist on dynamic variables predicting fluid responsiveness during laparoscopic surgery. The aim of this study was to explore the effects of laparoscopy on four dynamic variables: respiratory variations in pulse pressure (ΔPP), stroke volume variation by Vigileo/FloTrac (SVV (Vigileo) ), pleth variability index (PVI) and respiratory variations in pulse oximetry plethysmography waveform amplitude (ΔPOP), and their relation to fluid challenges during laparoscopic surgery. METHODS: ΔPP, SVV (Vigileo) , PVI and ΔPOP were studied in 20 adult patients before and during pneumoperitoneum (10-12 mmHg). During ongoing laparoscopic surgery, relations between the dynamic variables and changes in stroke volume oesophageal Doppler, (SV(OD) ) after fluid challenges (250 ml colloid) were evaluated. RESULTS: Pneumoperitoneum changed the dynamic variables as follows {mean [95% confidence interval (CI)]}: ΔPP 0.5 (-1.3, 2.3)%, P = 0.53; SVV (Vigileo) 0.6 (-1.3, 2.5)%, P = 0.52; PVI 2.9 (0.4, 5.3)%, P = 0.025. For ΔPOP, median difference (95% CI) was 2.5 (-0.15, 6.7)%, P = 0.058. During laparoscopic surgery, areas under receiver operating characteristics curves (95% CI) were ΔPP 0.53 (0.31-0.75), SVV (Vigileo) 0.74 (0.51-0.90), PVI 0.61 (0.38-0.81), ΔPOP 0.63 (0.40-0.82). Correlation coefficients (P-values) between changes in dynamic variables and changes in SV(OD) were ΔPP r = -0.65, P = 0.009; SVV (Vigileo) r = -0.73, P = 0.002; PVI r = -0.22, P = 0.44; ΔPOP r = -0.32, P = 0.24. CONCLUSION: ΔPP and SVV (Vigileo) did not change as pneumoperitoneum was established, whereas PVI increased and ΔPOP tended to increase. All four dynamic variables predicted fluid responsiveness relatively poor during ongoing laparoscopic surgery. ΔPP and SVV (Vigileo) tracked changes in stroke volume induced by fluid challenges during ongoing laparascopic surgery, whereas ΔPOP and PVI did not.

Photoplethysmographic and pulse pressure variations during abdominal surgery.

BACKGROUND: Respiratory variations in pulse pressure (ΔPP) predict fluid responsiveness during mechanical ventilation. Variations in pulse oximetry plethysmography amplitude (ΔPOP) are proposed as a non-invasive alternative. Large variations in ΔPOP and poor agreement between ΔPP and ΔPOP are found in intensive care unit patients. General anaesthesia is suggested to reduce variability of ΔPOP and improve agreement between the variables. We evaluated the variability of the agreement between and the diagnostic values of ΔPP and ΔPOP during ongoing open abdominal surgery. The variability of diagnostic methods in specific clinical conditions is important, as this reflects the stability over time during which clinical decisions are made. METHODS: Observational study during open abdominal surgery in general anaesthesia. ΔPP and ΔPOP were calculated semi-automatically from recording periods of approximately 5 min both before and after fluid challenges. Fluid responsiveness was evaluated by changes in stroke volume (oesophageal Doppler) after 250 ml colloid. RESULTS: Thirty-four fluid challenges were performed in 25 patients. Variance both within registration periods and between patients were significantly larger for ΔPOP than for ΔPP (54.1% vs. 22.1% and 69.6% vs. 22.6%, respectively, both P < 0.001). Limits of agreement with a regression-based correction were ± 13.9%. Areas under receiver operating characteristics curves for fluid responsiveness were 0.67 for ΔPP and 0.72 for ΔPOP. CONCLUSIONS: Analysis of raw signals during open abdominal surgery documents that the variance of ΔPOP is larger than of ΔPP, with wide limits of agreement between ΔPP and ΔPOP. The diagnostic values of ΔPP and ΔPOP are relatively poor.

Coronary reactivity in the porcine heart after short lasting myocardial ischaemia: effects of duration of ischaemia and myocardial stunning.

STUDY OBJECTIVE: The aim was to characterise reactive hyperaemia and endothelium dependent (ADP) and independent (adenosine) vasodilatation after ischaemic periods of increasing duration, and in the stunned myocardium. DESIGN: The left anterior descending coronary artery was occluded 5-7 cm distal from its origin for consecutive periods of 2, 2, 5, 10, and 2 min separated by 30 min of reperfusion. Coronary flow was continuously measured by Doppler flowmetry proximal to the occlusion site. ADP and adenosine were infused into the left coronary artery proximal to the flowprobe. EXPERIMENTAL MATERIAL: 11 domestic pigs, weight 25-36 kg, were used. MEASUREMENTS AND MAIN RESULTS: In the stunned myocardium maximal reactive hyperaemia after 2 min of ischaemia was preserved, whereas all other variables describing reactive hyperaemia were diminished: time to maximal hyperaemia by 40% (p less than 0.01), duration of hyperaemia by 44% (p less than 0.001), volume of hyperaemia by 53% (p less than 0.001), and repayment of flow debt by 43% (p less than 0.001). The vasodilating effects of ADP and adenosine (dose-response curves) were not altered after development of stunning. CONCLUSIONS: Preserved maximal hyperaemia and vasodilation during ADP and adenosine infusion, but reduced volume of hyperaemia, indicate normal coronary reactivity but diminished release in the stunned myocardium of the vasodilator(s) responsible for the prolonged postischaemic flow increase.

Reduced prostaglandin release from the stunned porcine heart--significance for attenuated reactive hyperaemia.

STUDY OBJECTIVE: Since both reactive hyperaemia and membrane phospholipids are altered even after short lasting ischaemic periods, the release of PGE2 and PGI2 in the basal state and during early reperfusion was examined to determine whether it was changed in the stunned myocardium. The effect of prostaglandin synthesis inhibition on reactive hyperaemia was also examined. DESIGN: The distal left anterior descending coronary artery was occluded for brief periods and coronary flow was recorded by Doppler flowmetry. In subgroups: (1) a shunt was established draining the ischaemic region for determination of myocardial prostaglandin release associated with 2 min of ischaemia before and after a 10 min occlusion; (2) prostaglandin synthesis was blocked between two 2 min occlusions by infusing indomethacin into the left anterior descending artery; and (3) segment lengths were measured in the left anterior descending artery region subjected to consecutive periods of 2, 10, and 2 min of ischaemia, and in a control region. EXPERIMENTAL MATERIAL: 21 pentobarbitone sodium anaesthetised pigs, weight 21-30 kg, were used. MEASUREMENTS AND MAIN RESULTS: 30 min after the 10 min occlusion, systolic shortening was reduced by 38(18-57)% (median +95% confidence interval; p less than 0.05). Concomitantly, basal PGE2 and PGI2 release was reduced by 69(30-77)% (p less than 0.05) and 58(7-81)% (p less than 0.05), respectively. During early reperfusion after 2 min of ischaemia, PGE2 release was reduced by 53(17-86)% (p less than 0.05) after development of stunning, whereas PGI2 release remained unaltered. Blockade of prostaglandin synthesis did not affect reactive hyperaemia either in normal or in stunned myocardium. CONCLUSIONS: Prostaglandin release from the stunned myocardium is reduced. Since indomethacin did not affect reactive hyperaemia, the attenuated PGE2 release during early reperfusion in stunned myocardium cannot explain the concomitant reduction in reactive hyperaemia.

Cardiac adaptation to one hour of mild regional low flow ischaemia in the pig.

OBJECTIVE: The aim was to determine the cardiac consequences of a 1 h period of mild regional low flow ischaemia in the pig heart. METHODS: In eight pentobarbitone sodium anaesthetised pigs (weight range 23-38 kg), the mid left anterior descending coronary artery was constricted by a hydraulic occluder. Transmural coronary blood flow (Doppler flowmetry) was reduced to approximately 70% of control for 1 h. After complete release of the occluder cardiac function was monitored for 2 h. Left ventricular segment lengths were continuously recorded in the region subjected to low flow ischaemia and in a control region supplied by the circumflex artery. RESULTS: After 1 h with a 28(SEM 3)% reduction in coronary blood flow, the systolic shortening index decreased from 100 to 68(7) (p < 0.001). This index transiently normalised upon reperfusion. Thereafter it declined, reaching a nadir of 72(5) at 1.25 h of reperfusion, and subsequently improved to 82(6) at 2 h of reperfusion. CONCLUSIONS: Normalisation of local myocardial function appears during the first minutes of reperfusion after 1 h of mild low flow ischaemia and is followed by a period of stunning.

ATP gated potassium channels in acute myocardial hibernation and reperfusion.

OBJECTIVE: ATP gated potassium (KATP) channels and adenosine are of crucial importance in coronary blood flow regulation and activation of KATP channels and adenosine receptor stimulation protect against infarction and development of stunning. The aim of this study was to test the hypothesis that opening of KATP channels and adenosine receptor stimulation are involved in perfusion-contraction matching, in acute hibernation, and in recovery after reperfusion. METHODS: 30 isolated piglet hearts (2-10 d old) and 20 isolated rabbit hearts were studied. The isolated piglet hearts were perfused with modified Krebs Henseleit (KH) solution enriched by washed human red blood cells; the isolated rabbit hearts were perfused with modified KH buffer. The effects of the KATP channel opener aprikalim (1 microM), the KATP channel antagonist glibenclamide (30 microM), and the adenosine receptor antagonist 8-(p-sulphophenyl)theophylline (SPT, 300 microM) on 2 h of low flow (10%) ischaemia and 1 h reperfusion were compared with saline in the piglet hearts. The effects of aprikalim (1 microM), glibenclamide (30 microM), and saline during 90 min of low flow (10%) ischaemia followed by 1 h reperfusion were also examined in the isolated rabbit hearts. RESULTS: At constant coronary flow aprikalim reduced perfusion pressure from 53(SEM 5) to 25(1) mm Hg (p < 0.001) in piglet hearts and from 55(5) to 39(5) mm Hg (p < 0.05) in rabbit hearts. Glibenclamide increased perfusion pressure from 47(5) to 61(6) mm Hg (p < 0.01) in piglet hearts and from 45(4) to 81(5) mm Hg (p < 0.001) in rabbit hearts. SPT increased perfusion pressure from 55(6) to 67(6) mm Hg (p < 0.05) in piglet hearts. Left ventricular systolic pressure remained unchanged in both models. During stepwise reductions in coronary flow a parallel stepwise reduction in left ventricular systolic pressure was observed in all groups. At 2 h of low flow ischaemia systolic pressure was 39(4)%, 37(5)%, 41(4)%, and 37(3)% of control for hearts treated with saline aprikalim, glibenclamide, and SPT, respectively. During the low flow period systolic pressure and MVO2 stabilised. An almost identical pattern occurred in rabbit hearts. After 30 min of recovery of piglet hearts left ventricular systolic pressure increased to 78(5)% (saline), 74(5)% (aprikalim), 84(5)% (glibenclamide), and 77(4)% (SPT) of control. The recovery as percentage of control in rabbit hearts was 63(11) (saline), 69(8) (aprikalim) and 56(13) (glibenclamide). CONCLUSION: Coronary vascular tone is highly responsive to KATP channel modulation and adenosine receptor blockade. KATP channels do not modulate either perfusion-contraction matching or acute hibernation and functional recovery during reperfusion in the red blood cell perfused piglet heart or the crystalloid perfused rabbit hearts. Moreover, adenosine receptor antagonism does not affect these phenomena in piglet hearts.

Importance of nitric oxide in canine femoral circulation: comparison of two NO inhibitors.

OBJECTIVE: The aim was to assess the importance of endothelium derived nitric oxide (NO) in the regulation of vascular tone in the limbs. Changes in the canine femoral circulation were investigated after inhibition of NO synthesis. METHODS: The effects of two NO inhibitors, NG-monomethyl-L-arginine (LNMMA) and NG-nitro-L-arginine (NOARG), were compared on basal femoral blood flow and on endothelium dependent (acetylcholine) and endothelium independent (glyceryl trinitrate) vasodilatation in 15 pentobarbitone anaesthetised mongrel dogs. An electromagnetic flow probe was placed on the femoral artery to measure femoral blood flow. One catheter was advanced into the femoral artery proximal to the flow probe for blood pressure recording and another catheter distal to the flow probe for drug infusions. RESULTS: LNMMA (0.28 mumol.ml-1) reduced basal femoral blood flow by 44(SEM 3)%, NOARG (0.07 mumol.ml-1) by 21(4)%, and NOARG (0.56 mumol.ml-1) by 29(3)%. The flow responses to acetylcholine were reduced after LNMMA by 27(8)%, unaltered after NOARG (0.07 mumol.ml-1), and reduced after NOARG (0.56 mumol.ml-1) by 60(7)%. The flow response to glyceryl trinitrate was unaltered. L-arginine re-established femoral blood flow after infusion of LNMMA and NOARG (0.07 mumol.ml-1), but L-arginine did not re-establish femoral blood flow after NOARG (0.56 mumol.ml-1), even when infused in a 60-fold molar excess. CONCLUSIONS: There is a continuous basal release of NO in the canine femoral circulation. The results obtained by infusing LNMMA suggest that more than 40% of basal femoral blood flow is mediated by endothelium derived NO. Whereas LNMMA was more potent than NOARG in reducing basal NO release, NOARG (0.56 mumol.ml-1) reduced acetylcholine induced vasodilatation by as much as 60%.

Release of endothelin from the porcine heart after short term coronary artery occlusion.

OBJECTIVE: Endothelin is increased in plasma following myocardial infarction. Whether brief periods of myocardial ischaemia not leading to myocardial infarction increase plasma endothelin is not known. Thus, the present study was designed to examine cardiac endothelin balance in association with a 10 min coronary artery occlusion followed by reperfusion. METHODS: Venous blood was selectively sampled from the transiently ischaemic myocardium using a shunt between the anterior interventricular vein and the right atrium in eight pentobarbitone anaesthetised pigs. Flow in the shunt was measured with a Doppler flow probe. Arterial blood was drawn from the aortic arch. Plasma endothelin was measured using an Endothelin 1-21 specific [125I] assay system. This assay system has no cross reactivity with big endothlin. RESULTS: A net cardiac endothelin uptake of 0.7(0.3-1.4) fmol.min-1 x g-1 (median, 95% confidence interval) in the control period shifted to a net release during the first 10 min of reperfusion. The release reached a maximum of 2.8(0.4-6.0) fmol.min-1 x g-1 after 1.5 min of reperfusion. Cardiac venous endothelin concentration increased from 3.4(2.5-4.8) to 4.4(3.6-6.9) and 4.4(3.6-6.6) fmol.ml-1 at 1.5 and 5 min of reperfusion, respectively (p < 0.001 for both). Arterial endothelin concentration decreased from 4.8(3.9-6.1) to 2.7(2.4-4.3) fmol.ml-1 at 10 min of reperfusion (p < 0.001). CONCLUSION: Endothelin is released from the heart for several minutes during reperfusion following a brief coronary artery occlusion.

Alterations in plasma endothelin during passage through the left heart chambers before and after brief myocardial ischaemia.

OBJECTIVE: Although the lung can both produce and extract endothelin, its role in regulating plasma endothelin is not settled. Whether the endocardium is able to affect plasma endothelin is also unknown. The first aim of this study was to examine if endothelin concentration in plasma changes when passing through the pulmonary circulation or the left heart chambers. A marked decrease in endothelin concentration has been shown to occur in the aortic arch during early reperfusion following a 10 min mid left anterior descending coronary artery occlusion. A second aim was therefore to investigate whether this decrease was due to removal of endothelin in the pulmonary circulation or through the left heart chambers. METHODS: In seven open chest, pentobarbitone anaesthetised pigs blood was obtained from the pulmonary artery, the left atrium, and the aortic arch at control conditions and at 10 and 20 min reperfusion following a 10 min coronary occlusion. Endothelin measurements were performed using an endothelin 1-21 specific [125I] assay system (RPA 555). RESULTS: At control conditions there was no difference in endothelin concentration in blood obtained from the pulmonary artery [3.9 (2.7-5.2) fmol.ml-1, median (95% confidence interval)] and the left atrium [3.8 (2.8-5.8) fmol.ml-1], whereas there was a significantly higher endothelin concentration in the aortic arch [4.9 (3.8-7.2) fmol.ml-1]. At 10 min reperfusion following the 10 min coronary occlusion there was still no difference in endothelin concentration between the pulmonary artery [4.3 (2.8-6.0) fmol.ml-1] and the left atrium [4.1 (2.7-5.7) fmol.ml-1]. However, in contrast to the increase observed before myocardial ischaemia, the endothelin concentration was significantly reduced in the aortic arch [2.8 (2.4-4.4) fmol.ml-1] compared to the left atrium. At 20 min reperfusion, all endothelin concentrations had returned to preischaemic values. CONCLUSIONS: These findings suggest a role for the left heart chambers in regulating the endothelin concentration in blood entering the aorta.

Free radical scavenging enzymes and G protein mediated receptor signalling systems in ischaemically preconditioned porcine myocardium.

OBJECTIVE: Increased antioxidant defence and altered G protein mediated receptor signalling systems could be expected in myocardial preconditioning. The myocardial antioxidant defence and the integrity of the G protein mediated receptor signalling systems were therefore examined in normal and preconditioned myocardium. METHODS: Preconditioning in the porcine heart was induced by two occlusions of the mid left anterior descending coronary artery for 10 min, with a 30 min reperfusion interval. Left ventricular biopsies were obtained from control and preconditioned regions 30 min after the last occlusion. RESULTS: In biopsies from the preconditioning region, neither the activities of superoxide dismutase of glutathione peroxidase, nor the content of malondialdehyde were changed. There were no alterations in either the number of receptors (beta adrenergic, muscarinic and endothelin receptors) or the amount of G proteins. Furthermore, the activity of adenylyl cyclase remained unchanged. CONCLUSIONS: No change in the antioxidant defence was demonstrated in preconditioned myocardium. This finding does not support the hypothesis that increased antioxidant defence could contribute to the cardioprotection of preconditioning. Additionally, an intact G protein mediated receptor signalling system was found in preconditioned myocardium with regard to beta adrenergic, muscarinic, and endothelin receptors.

A new approach to normalize myocardial temperature in the open-chest pig model.

To prevent unphysiological temperature fluctuations in the myocardium in the open-chest model, we constructed a thermocage. Five pigs under pentobarbital sodium anesthesia underwent repetitive left anterior descending (LAD) coronary artery occlusions. Myocardial temperature was measured without any thoracic temperature-controlling device and in the presence of either a heating lamp or the thermocage. Without any thoracic temperature-controlling device, the temperature at 5-mm myocardial depth was 1.28 +/- 0.33 degrees C below the intra-abdominal temperature (P < 0.05). During a proximal 5-min LAD occlusion, myocardial temperature decreased by 1.86 +/- 1.02 degrees C in the ischemic area (P < 0.05). Both the heating lamp and the thermocage abolished the difference between intra-abdominal and myocardial temperatures and prevented the decrease in myocardial temperature during ischemia. Only the thermocage minimized myocardial temperature fluctuations due to air currents and prevented epicardial exsiccation. We conclude that either a thermocage or a heating lamp may be used to normalize myocardial temperature in the open-chest pig model. However, the thermocage is superior to the lamp in minimizing temperature fluctuations and preventing epicardial exsiccation.

Effect of heart transplantation on impaired peripheral microvascular perfusion and reactivity in congestive heart failure.

Whether reduced peripheral blood flow in congestive heart failure is reversed after heart transplantation, has not been closely examined. We therefore studied skin microvascular resting perfusion and reactivity in patients pre- and postoperatively. Resting digital skin perfusion, together with the responses to cold pressor test, postocclusive reactive hyperemia and direct skin heating were examined with laser Doppler perfusion measurements. We examined 28 patients with congestive heart failure and 14 of these patients after heart transplantation and compared them to 13 healthy controls. Measurements were performed within 3 months preoperatively and 12 days, 1, 2, 3 and 6 months postoperatively. Patients with congestive heart failure had significantly lower resting perfusion levels than controls and demonstrated attenuated responses to both stimuli of vasodilation (all P<0.01). While peak hyperemic responses improved significantly after transplantation, postocclusive area under the hyperemic curve decreased further, and none of these variables were normalized after 6 months. In contrast, minimal perfusion during cold pressor test increased from a significantly lower level in the patients with congestive heart failure (P<0.05), to a level similar to that of the controls within 12 days postoperatively. Thus, skin microvascular perfusion and reactivity improve, but are not normalized within 6 months of transplantation. Both pre- and postoperative factors may be involved in maintaining a dysfunction of the peripheral microcirculation, which may contribute to exercise intolerance and hypertension in heart transplant recipients.

Importance of heart rate for acute hibernation in isolated blood-perfused piglet hearts.

BACKGROUND: Hibernating myocardium may benefit from revascularization. There are several experimental models for acute hibernation. In intact hearts low-flow ischemia causes time-dependent metabolic alterations, termed "metabolic adaptation". In isolated heart preparations metabolic responses to low-flow ischemia vary, and signs of metabolic adaptation are not consistently found. In isolated hearts global ischemia may cause bradycardia unless the hearts are paced. We hypothesized that the lack of consistent metabolic adaptation to low-flow ischemia in isolated hearts might be due to bradycardia during ischemia. In this study we investigated the influence of heart rate on metabolism and function in an isolated heart preparation. METHODS: Isolated blood-perfused piglet hearts were subjected to 120 min 10% flow. In groups A (n=9) and B (n=4) hearts were not paced during ischemia, in groups C (n=5) and D (n=5) hearts were paced at pre-ischemic heart rate during ischemia. RESULTS: Without pacing, heart rate declined to approximately 1/3 during ischemia and anaerobic metabolism showed a slight decline over time. With pacing, production of protons, pCO2 and lactate showed a bell-shaped curve which peaked at 20-25 min of ischemia, followed by a subsequent decline towards the end of ischemia (overall p < 0.001 for all). However, reperfusion revealed impaired recovery of function in paced hearts compared to non-paced hearts (53 +/- 7% vs 77 +/- 4%, p < 0.05) concomitant with higher release of creatine kinase (455 +/- 93 IU/100 g vs 106 +/- 13 IU/100 g, p < 0.01). CONCLUSIONS: When heart rate is allowed to decline during low-flow ischemia in isolated piglet hearts, signs of metabolic adaptation are not evident. When hearts are paced during ischemia time-dependent alterations in anaerobic metabolism occur, resembling observations seen in intact beating hearts. However, paced hearts also show indications of increased cellular injury, indicating that in paced hearts the metabolic consequences are mostly due to increased irreversible cell injury. Thus, the model for acute hibernation with 10% flow in isolated blood-perfused piglet hearts are critically dependent on bradycardia during ischemia.

Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine.

The present study was performed to compare haemodynamic variables at baseline and the incidence of ventricular fibrillation during the early phase of ischaemia in swine during pentobarbital or medetomidine-ketamine-fentanyl anaesthesia. Twenty-two swine (mean +/- SD: 29+/- 3 kg) were anaesthetized with sodium pentobarbital (induction with 36 mg/kg intraperitoneally, and maintenance with 5-20 mg/kg/h intravenously [i.v.]) and 6 swine (27+/- 3 kg) were anaesthetized with ketamine and fentanyl (premedicated with medetomidine 0.1 mg/kg and ketamine 10 mg/kg intramuscularly, induction with ketamine 20 mg/kg and fentanyl 0.025 mg/kg i.v., and maintenance with ketamine 20 mg/kg/h and fentanyl 0.025 mg/kg/h i.v.). After a stabilization period of 30 min, the left anterior descending coronary artery (LAD) was occluded for 10 min. Haemodynamic data and occurrence of ventricular fibrillation were recorded. The ischaemic area was measured by fluorescing microspheres. Swine anaesthetized with medetomidine-ketamine-fentanyl had significantly lower heart rate, myocardial contractility, peak left ventricular pressure, arterial blood pressure, aortic blood flow, myocardial blood flow and cardiac index at baseline, than swine anaesthetized with pentobarbital. Whereas none of the swine anaesthetized with pentobarbital fibrillated during the LAD occlusion, ventricular fibrillation occurred in 83% of the animals anaesthetized with medetomidine-ketamine-fentanyl (P< 0.001). No significant difference was found in size of ischaemic area between the two groups. Thus, we show a depression in haemodynamic variables at baseline and a higher incidence of ventricular fibrillation during the early phase of ischaemia in swine anaesthetized with medetomidine-ketamine-fentanyl compared to swine anaesthetized with pentobarbital.

Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all), respectively. CONCLUSION: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

[The hibernating myocardium]. / Det hibernerende myokard.

The hibernating myocardium refers to the presence of persistent myocardial and left ventricular dysfunction at rest, due to reduced coronary blood flow. This left ventricular dysfunction represents an endogenous adaptive mechanism which prevents irreversible cell damage. The dysfunction in hibernating myocardium improves following restoration of coronary blood flow. A key concept in hibernating myocardium is that the reduction in contractile function induced by ischaemia has a protective effect. By reducing oxygen demand the myocardium maintains its viability in the setting of limited oxygen supply. The hibernating myocardium is a new metabolic state that is a consequence of an ischaemic condition, but the hibernating cardiomyocytes are not necessarily ischaemic. There are no adequate animal models for chronic hibernation. However, there are models for acute hibernation both in intact beating hearts and in isolated hearts. In these models a stable reduction in mechanical function for some hours has been demonstrated, whereas metabolic indicators of ischaemia improve during sustained low-flow ischaemia.