Biomedical subjects

K A Kirkebøen

Publications and source records attributed to K A Kirkebøen.

At least 19 recordsLinked to original sources

PubMed2007

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.

Adult↗

PubMed2004

Sevoflurane-induced malignant hyperthermia during cardiopulmonary bypass and moderate hypothermia.

A 56-year old man was admitted for elective mitral valve repair and coronary artery bypass surgery due to mitral valve leakage and unstable angina. After induction of anaesthesia he developed a combined metabolic and respiratory acidosis. Different diagnosis were considered and we decided to treat the patient with dantrolene due to suspicion of malignant hyperthermia (MH). The patient received one dose of dantrolene 2,5 mg/kg during cardiopulmonary bypass (CPB) and a second dose of dantrolene 2,5 mg/kg during weaning from CPB. The first arterial blood gas sample taken in the intensive care unit showed relapse of the acidosis and we administered an infusion of 150 mg dantrolene over 3 hours. The patient gradually recovered without sequel and MH was verified by muscle biopsy testing.

Anesthetics, Inhalation↗

PubMed2004

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.

Anesthesia↗

PubMed2000

Adenosine and cardioprotection during ischaemia and reperfusion--an overview.

Adenosine is a local hormone, with numerous tissue-specific biological functions. In the myocardium, adenosine is released in small amounts at constant basal rate during normoxia. During ischaemia the production of adenosine increases several fold due to breakdown of adenosine triphosphate (ATP). Increased production of adenosine causes coronary vasodilatation. Thus, adenosine couples myocardial metabolism and flow during ischaemia and is called a homeostatic or "retaliatory metabolite". Furthermore, adenosine has electrophysiological effects in supraventricular tissue, causing a decrease in heart rate. In 1985 it was discovered that adenosine also exerts cardioprotective effects directly on cardiomyocytes. The aim of this review is to give an overview of the role of adenosine as a directly cytoprotective agent during myocardial ischaemia and reperfusion. We will focus on its effects on the myocytes, elicited by stimulation of adenosine receptors in sarcolemma, which triggers intracellular signalling systems. We will also address the new aspect that adenosine can influence regulation of gene expression. There is evidence that the myocardium is capable of endogenous adaptation in response to ischaemia, namely "hibernation" and early and late phases of "preconditioning". Endogenous substances produced during ischaemia probably trigger these responses. We will discuss the role of adenosine in these different settings. Adenosine can be given exogenously through intravasal routes; however, this review will also focus on the effects of endogenously produced adenosine. We will discuss pharmacological ways to increase endogenous levels of adenosine, and the effects of such interventions during ischaemia and reperfusion. Finally, we will review results from studies in humans together with relevant experimental studies, and indicate potential therapeutic implications of adenosine.

Adenosine↗

PubMed2000

Nitric oxide indices in human septic shock.

OBJECTIVES: To study the relation between nitrite, nitrate, nitrotyrosine, and nitrosothiols as NO indices in human septic shock. DESIGN: A prospective clinical study. SETTING: Intensive care units in a university hospital and a central county hospital. PATIENTS: Sixteen patients admitted for septic shock. Nine healthy volunteers served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock had a hyperdynamic circulatory response and required infusion of at least two vasopressors to maintain systemic blood pressure. Four episodes of recurrent shock occurred in two patients. Heparinized plasma was collected once daily for analysis of NO indices. Peak plasma concentrations of nitrite + nitrate (NOx) were elevated in first episodes of septic shock; 144+/-39 microM vs. controls, 20+/-3 microM (p < .05). Peak plasma NOx concentrations in recurrent shocks were; 160+/-19 microM. Peak plasma concentrations of 3-nitrotyrosine (NT) were elevated in primary septic shock 102+/-19 pmol x mL(-1) vs. controls 14+/-6 pmol x mL(-1) (p < .05). Peak NT concentrations were 117+/-37 pmol x mL(-1) in recurrent septic shock. Peak plasma NT concentrations did not coincide with peak NOx concentrations in half of the episodes of septic shock. Plasma NT was elevated (59+/-15 pmol x mL(-1) vs. controls 14+/-6 pmol x mL(-1), p < .05) in patients with normal plasma NOx concentrations throughout septic shock. Plasma concentrations of nitrosothiols did not change during septic shock. CONCLUSIONS: Plasma concentrations of NOx and NT are elevated in primary episodes of septic shock and may also be elevated in secondary septic shock, but too few episodes of recurrent septic shock occurred to allow firm conclusions. Plasma concentrations of NT are elevated in patients with septic shock with normal plasma NOx concentrations, indicating that plasma concentrations of NOx may not always accurately reflect NO production. Reactive nitrogen species may be formed in septic shock, and measuring both NOx and NT may give a better indication of NO production in septic shock than NOx alone. Plasma levels of nitrosothiols did not change during septic shock.

Adolescent↗

PubMed2000

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.

Acute Disease↗

PubMed1999

[Nitric oxide--basal biochemistry and physiological aspects].

Nitric oxide (NO) is a naturally occurring molecule found in a variety of cell types and organ systems, including the cardiovascular, immune and nervous system. NO is normally produced in the endothelium from L-arginine by the constitutive isoform of the NO synthase (cNOS). Thereby, NO is an important regulator of vascular tone, prevents platelet adhesion, aggregation and activation, limits leukocyte adhesion to the endothelium and regulates myocardial contractility. This physiological production of NO is important for blood pressure regulation, blood flow distribution and tissue perfusion. Following injury or certain inflammatory stimuli, the expression of an inducible NO synthase (iNOS) can occur in a great variety of cells. In the last decade research on NO has suggested new treatment strategies for several diseases. In this review we discuss the biochemistry of NO and its basal physiological implications, with special emphasis on NO produced in the endothelium.

Animals↗

PubMed1999

[Nitric oxide--an important mediator in sepsis?].

Animal experiments suggest that hyperproduction of nitric oxide (NO) by the inducible isoform of the enzyme NO synthase (iNOS) may contribute to hypotension, cardiodepression and vascular hyporeactivity in septic shock. Lipopolysaccarides and cytokines, like tumor necrosis factor, interleukin-1 and interferon-gamma, have been shown to induce iNOS in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. In several animal models of septic shock, treatment with inhibitors of NO synthesis has been shown to improve haemodynamic variables and survival. In human septic shock, inhibition of NO synthesis has been shown to alter haemodynamic variables in short term studies. However, a large multicentre study was recently stopped due to increased mortality in patients in septic shock treated with the NO synthase inhibitor NG-monomethyl-L-arginine. The aim of this review is to discuss the role of NO in sepsis and the potential therapeutic implications of NO as a target in treatment of human septic shock. We emphasize that many septic patients have preexisting endothelial dysfunction or lung diseases, which may predispose to severe adverse effects during systemic inhibition of NO synthesis. We also focus on the lack of direct evidence for iNOS expression in human septic shock and on the discrepancy between animal and human data.

Animals↗

PubMed1999

[Endothelial function in coronary atherosclerosis and heart failure--the role of nitric oxide in regulation of vasomotor tone].

The endothelium plays a pivotal role in synthesizing biologically active substances that modulate the vascular tone of underlying smooth muscle cells. Assessment of endothelial function requires measurement of the effects of endothelium-dependent and -independent vasodilators on the systemic microcirculation or resistance vessels. Endothelial dysfunction has been demonstrated early in the course of coronary artery disease, both by studying vasomotor responses in coronary and peripheral vessels, and in the peripheral circulation of patients with chronic heart failure. The impairment of endothelium-dependent vasodilation is related to an abnormality in the endothelium-derived nitric oxide system. The evolving understanding of the complex and probably multifactorial underlying molecular mechanisms of endothelial dysfunction has lead to the identification of potential beneficial therapeutic interventions. Restoration of endothelial function has been associated with fewer episodes of ischaemia in coronary artery disease and improved exercise capacity in heart failure. In light of recent studies we discuss the role of the endothelium, with special emphasis on nitric oxide, in the regulation of vascular tone in coronary artery disease and heart failure.

Animals↗

PubMed1999

Elevated levels of endogenous adenosine alter metabolism and enhance reduction in contractile function during low-flow ischemia: associated changes in expression of Ca(2+)-ATPase and phospholamban.

Adenosine has several potentially cardioprotective effects including vasodilatation, reduction in heart rate and alterations in metabolism. Adenosine inhibits catecholamine-induced increase in contractile function mainly through inhibition of phosphorylation of phospholamban (PLB), the main regulatory protein of Ca(2+)-ATPase in sarcoplasmic reticulum (SR), and during ischemia it reduces calcium (Ca2+) overload. In this study we examined the effects of endogenous adenosine on contractile function and metabolism during low-flow ischemia (LFI) and investigated whether endogenous adenosine can alter expression of the Ca(2+)-ATPase/PLB-system and other Ca(2+)-regulatory proteins. Isolated blood-perfused piglet hearts underwent 120 min 10% flow. Hearts were treated with either saline, the adenosine receptor blocker (8)-sulfophenyl theophylline (8SPT, 300 micromol/l) or the nucleoside transport inhibitor draflazine (1 micromol/l). During LFI, 8SPT did not substantially influence metabolic or functional responses. However, draflazine enhanced the reduction in heart rate, contractile force and MVO(2), with less release of H+ and CO2. Before LFI there were no significant differences between groups for any of the proteins (Ca(2+)-ATPase, ryanodine-receptor, Na+/K(+)-ATPase) or mRNAs (Ca(2+)-ATPase, PLB, calsequestrin, Na+/Ca(2+)-exchanger) measured. At end of LFI mRNA-level of PLB was higher in draflazine-treated hearts compared to both other groups (P<0.01 vs both). Also, at end of LFI protein-level of Ca(2+)-ATPase was lower in draflazine-treated hearts (P<0.05 vs both), and a parallel trend towards a lower mRNA-level was seen (P=0.11 vs saline and P=0.43 vs 8SPT). During LFI tissue Ca2+ tended to rise in saline- and 8SPT-treated hearts but not in draflazine-treated hearts (at end of LFI, P=0.01 vs 8SPT). We conclude that the amount of adenosine normally produced during LFI does not substantially influence function and metabolism. However, increased endogenous levels by draflazine enhance downregulation of function and reduce signs of anaerobic metabolism. At end of LFI associated changes in expression of PLB and Ca(2+)-ATPase were seen. The functional significance was not determined in the present study. However, altered protein-levels might influence Ca(2+)-handling in sarcoplasmic reticulum and thus affect contractile force and tolerance to ischemia.

Adenosine↗

PubMed1999

The role of nitric oxide in sepsis--an overview.

Nitric oxide (NO) is normally produced in the endothelium by the constitutive isoform of the NO synthase. This physiological production of NO is important for blood pressure regulation and blood flow distribution. Several lines of evidence suggest that a hyperproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardiodepression and vascular hyporeactivity in septic shock. Lipopolysaccarides and cytokines, such as tumor necrosis factor, interleukin-1 and interferon-gamma, have been shown to induce iNOS in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. Treatment with inhibitors of NO synthesis has been shown to improve hemodynamic variables and survival in several animal models of septic shock. In human septic shock, inhibition of NO synthesis has been shown to alter hemodynamic variables in short-term studies, but it is uncertain whether this treatment has beneficial long-term effects. The aim of this review is to give an overview of the physiological role of NO and to discuss the role of NO in sepsis and the potential therapeutic implications of NO as a target in treatment of human septic shock. A main new aspect of this review is a critical discussion of previous reports measuring plasma nitrite/nitrate during septic shock and an evaluation of the validity of interpreting these data as evidence for a hyperproduction of NO. This review also emphasizes that many septic patients have preexisting endothelial dysfunction and lung diseases, which may contribute to adverse effects by systemic inhibition of NO synthesis. Another new aspect of the present review is a focus on the lack of direct evidence of iNOS expression in human septic shock.

Animals↗

PubMed1998

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.

Adult↗

PubMed1998

[Receptor mediated effects of adenosine and caffeine].

Adenosine consists of one ribose and one purine moiety and binds to specific receptors on cell membranes. The receptors are coupled to G-proteins and additionally to various effector-systems. When a mismatch occurs between energy supply and energy demand, adenosine is produced by the catabolism of adenosine triphosphate. The metabolism of an organ is thereby coupled to the local blood supply (metabolic vasodilation). In addition to vasodilation, adenosine has several electrophysiological, cardioprotective, metabolic, and antiinflammatory properties. Adenosine is rapidly metabolized in blood and interstitial fluid, through cell absorption and degradation by adenosine deaminase. The short half-life of adenosine limits its clinical value. However, there are several ways of increasing the interstitial concentration of adenosine. At present, adenosine or adenosine-potentiating substances are used clinically to terminate supraventricular tachycardias, to induce myocardial ischemia in patients who are unable to exercise, and to reduce myocardial ischemia or reperfusion injury. Caffeine and other methylxanthines are adenosine receptor antagonists, and several of the pharmacodynamic properties of these substances are caused by adenosine receptor antagonism.

Adenosine↗

PubMed1998

Spectral analysis of the laser Doppler perfusion signal in human skin before and after exercise.

Spectral analysis based on wavelet transformation of the periodic oscillations of the cutaneous laser Doppler flowmetry (LDF) signal was used to analyze exercise-induced changes in flow motion in humans. The measurements were performed on the forearm skin in nine healthy, less-trained subjects before and after exercise. Periodic oscillations with frequencies of around 1, 0.3, 0.1, and 0.04 Hz were demonstrated, which are proposed to represent the influence of heart beat, respiration, intrinsic myogenic activity, and the neurogenic factors, respectively, on cutaneous blood flow. We also demonstrated oscillations with a frequency of around 0.01 Hz both before and after exercise. The mean spectral amplitude in the frequency range from 0.0095 to 2.3 Hz increased twofold (P = 0.004) in response to exercise. This increase results from a significant increase in the amplitude of oscillations of around 1, 0.3, and 0.1 Hz. The amplitude of oscillations of around 1 and 0.3 Hz increased onefold in response to exercise (P = 0.02 for both frequencies), whereas the amplitude of oscillations of around 0.1 Hz increased threefold (P = 0.008). Furthermore, to evaluate relative changes of each particular oscillation in response to exercise, the absolute amplitude of each frequency interval was divided by the mean spectral amplitude. In this way, the relative contribution of oscillations of around 0.01 and 0.04 Hz were shown to decrease significantly following exercise (P = 0.008 and P = 0.004, respectively). The relative contribution of the oscillations of around 0.1 Hz increased, although not statistically significant (P = 0.08), while the relative contribution of the oscillations of around 0.3 and 1 Hz to the total flow motion remained unchanged in response to exercise (P = 0.84 and P = 0.95, respectively). These findings indicate an increased contribution of the oscillations of around 0.1 Hz to the regulation of the cutaneous blood flow following exercise, whereas oscillations of around 0.04 and 0.01 Hz contribute less. We conclude that spectral analysis using a wavelet transformation of the LDF signal is a valuable tool for use in the evaluation of exercise-induced changes in the dynamics of cutaneous microvascular blood flow, but further studies are necessary to clarify the physiological origin of these oscillations.

Exercise↗

PubMed1998

Characterization of metabolic responses to low-flow ischemia in intact pig hearts and isolated blood-perfused neonatal pig hearts.

UNLABELLED: There are different well established experimental models of low-flow ischemia. We examined metabolic variables during reduced coronary blood flow (CBF) in intact pig hearts and isolated neonatal pig hearts, producing similar degrees of postischemic dysfunction without infarction. The isolated hearts were perfused with red blood cell enriched buffer. In eight open-chest pigs mid-LAD flow was reduced to 70% for 60 min, followed by 120 min reperfusion. Myocardial segment lengths were recorded and regional coronary venous blood was sampled. In isolated piglet hearts CBF was reduced to 50% (n = 4), 25% (n = 4), and 10% (n = 17). Only when flow was reduced to 10% did hearts show signs of anaerobic metabolism. Mechanical function was recorded by a balloon in the left ventricle and coronary venous blood was sampled. Intact pig hearts showed release of protons, CO2, and lactate which peaked after 5-10 min of ischemia and thereafter stabilized at reduced levels. In contrast, in isolated neonatal hearts exposed to 10% CBF releases of protons, CO2, and lactate were stable during ischemia with no adaptational changes over time. In a separate group (n = 4), repetitive biopsies revealed no adaptational changes over time for adenosine triphosphate and creatine phosphate during 10% CBF. Contractile function was stably reduced during ischemia in both models. CONCLUSION: During reduced CBF "metabolic adaptation" occurs in intact pig hearts. In contrast, this feature is not present in isolated blood-perfused piglet hearts. The mechanisms responsible for these differences are uncertain. However, differences in metabolism between adult and neonatal hearts and different loading conditions during ischemia might contribute.

Adaptation, Physiological↗

PubMed1998

Enhanced endothelium-dependent vasodilatation in human skin vasculature induced by physical conditioning.

Functional alterations to the endothelial cells of the vascular system may contribute to the improved circulatory performance induced by physical conditioning. We evaluated microvascular reactivity to iontophoretic application of acetylcholine (ACh) and sodium nitroprusside (SNP) through the skin and blood perfusion measurements in the same area using laser Doppler flowmetry. Whereas ACh acts on smooth muscle cells of the vascular system via the production of vasodilator substances from the endothelium, SNP is an endothelium-independent vasodilator acting on vascular smooth muscle cells directly. The study was performed using two groups of subjects with different levels of aerobic endurance, long distance runners competing at national level (n = 9) and controls (n = 9). The subjects were tested for 40 min on a treadmill before and after an exercise test at 80% of their maximal oxygen uptake. During stimulation by ACh cutaneous perfusion increased to a higher level in the athletes than in the controls (overall P<0.05), whereas an acute period of exercise abolished this difference (overall P>0.6). There was no significant difference between the athletes and the controls with respect to the SNP-induced increase in cutaneous perfusion either before (P>0.9) or after (P>0.9) exercise. The higher cutaneous perfusion responses to stimulation with ACh in the athletes than in the controls may support the hypothesis that regular exercise modifies the responsiveness of the cutaneous endothelium. The difference in ACh-induced perfusion and in unstimulated forearm perfusion between the two groups was present only at rest. This finding indicated that mechanisms were introduced during exercise, which compensated for the lower endothelial sensitivity to stimulation in the controls at rest.

Acetylcholine↗

PubMed1998

N(G)-monomethyl-L-arginine improves survival in a pig model of abdominal sepsis.

OBJECTIVE: To test the effect of a continuous infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on survival rate and hemodynamics in a pig model of endogenous peritoneal live bacterial sepsis. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-five pigs with an average weight of 26 kg (range 21 to 33). INTERVENTIONS: After surgical preparation, animals (control, n=6) given anesthesia and fluids were observed for 9 hrs. Fifteen experimental animals received 0.5 g of cecal content/kg of body weight intraperitoneally after surgery. Nine of these animals received standard anesthesia and fluids and were observed for 9 hrs or until death. Six animals received a continuous infusion of L-NMMA (10 mg/kg/hr) 3 hrs after sepsis induction. Starting 3 hrs after surgery, five nonrandomized animals were given anesthesia and fluids and received a 6-hr continuous infusion of L-NMMA (10 mg/kg/hr). An additional nine animals were anesthetized and blood samples were taken to determine plasma nitrate concentrations in nonoperated pigs. MEASUREMENTS AND MAIN RESULTS: L-NMMA treatment increased 9-hr survival in septic animals from 11% to 83% (p < .001), prevented a further decrease in mean arterial pressure and restored mean arterial pressure to control levels (p < .00002 vs. nontreated septic animals). Mean pulmonary arterial pressure increased slightly during L-NMMA infusion (p < .0003). Coronary blood flow was preserved during L-NMMA treatment. Cardiac index and urine production reached and maintained control levels during L-NMMA treatment of septic animals. Mean central venous pH did not deteriorate during L-NMMA treatment. Animals treated with L-NMMA had plasma nitrate concentrations similar to nonseptic control animals. The results from the nonseptic control group receiving L-NMMA suggest that a substantial part of the effect of L-NMMA in this model of septic shock may be due to inhibition of the constitutive nitric oxide production. CONCLUSIONS: In this porcine model of peritoneal sepsis, infusion of L-NMMA increased survival rate and maintained mean arterial pressure without worsening tissue oxygenation. Coronary blood flow, cardiac index, systemic vascular resistance, and urine production were well maintained during L-NMMA treatment.

Animals↗

PubMed1997

Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts.

BACKGROUND: Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. METHODS AND RESULTS: Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P<.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P<.05). CONCLUSIONS: In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.

Adenosine↗