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PubMed1999

Severe stenosis of the internal carotid artery presenting as loss of consciousness due to the presence of a primitive hypoglossal artery: a case report.

BACKGROUND: Symptoms of ischemic attacks in the internal carotid system usually involve focal cerebral dysfunction, i.e., hemiparesis or aphasia. However, an ischemic attack in the vertebrobasilar artery system usually presents with combined symptoms. The variety of manifestations included in the vertebrobasilar profile makes the potential pattern of symptoms considerably more variable and complex than that in the carotid system. Manifestations can include syncope and also vertigo. METHOD AND RESULTS: A 42-year-old woman experienced frequent attacks of faintness with vertigo. Angiography demonstrated severe stenosis of the left internal carotid artery with a persistent primitive hypoglossal artery just distal to the stenosis. The right internal carotid artery was normal and cross circulation through the anterior communicating artery was not well developed. Both vertebral arteries were hypoplastic. The patient underwent carotid endarterectomy and, thereafter the episodes of syncope completely disappeared. CONCLUSION: It was supposed that global ischemia including the brain stem occurred because of stenosis of the left internal carotid artery attributable to the presence of a primitive hypoglossal artery.

Adult↗
PubMed2001

Downregulation of myocardial contractility via intact ventriculo--arterial coupling in the brain dead organ donor.

OBJECTIVE: To test the hypothesis that altered loading conditions play a key role in hemodynamic instability and cardiac dysfunction in the brain dead (BD) organ donor. METHODS: BD was induced by inflation of a subdural balloon catheter. In the first part of the study, left ventricular function was assessed in a canine in situ cross-circulated heart model (n=6). Pre- and afterload and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In the second part of the study, hearts (n=6) were investigated in vivo allowing the interaction between left ventricular contractility and arterial load. Left ventricular pressure--volume loops were obtained by a combined conductance-pressure catheter and the slope of the endsystolic pressure--volume relationship (Ees), arterial elastance (Ea), stroke work (SW), pressure--volume area, ventriculo--arterial coupling ratio (VAC) and mechanical efficiency (Eff) were calculated. RESULTS: Induction of BD led to a hyperdynamic response in both models with a significant increase of most hemodynamic parameters. In the in situ isolated heart model, left ventricular contractility returned to baseline without any further deterioration. In contrast, in the intact circulation the hemodynamic parameters declined significantly in comparison to baseline 4 h after BD (Ees: 4.07+/-0.51 vs. 8.06+/-1.09 mmHg/ml, P<0.05, Ea: 3.17+/-0.39 vs. 4.42+/-0.30 mmHg/ml, P<0.05). However, VAC (0.78+/-0.09 vs. 0.65+/-0.14 n.s.) and Eff (73.4+/-2.1 % vs. 76.8+/-3.7 %, n.s.) remained constant over the time. CONCLUSION: BD induction leads to an initial hyperdynamic reaction followed by hemodynamic instability. The facts that no cardiac dysfunction occurred if loading conditions were kept constant and the ventriculo--arterial coupling ratio and mechanical efficiency remained constant in the intact animal model indicate that decreased contractility reflects to decreased arterial elastance after brain death. Therefore, reduced contractile function after brain death at a decreased afterload may contribute to stroke work optimization.

Animals↗
PubMed2000

Role of neural and humoral factors in hyperdynamic reaction and cardiac dysfunction following brain death.

BACKGROUND: Although hemodynamic instability and cardiac dysfunction after brain death are reported in the potential organ donor, the underlying mechanisms, for example, neurohumoral changes, myocardial injury, and altered loading conditions, have not been differentiated in clinical and experimental settings. In the present study, we performed a load-independent analysis of cardiac function, focusing on the influence of brain death-associated neural and humoral factors. METHODS: In a canine in situ cross-circulated heart model, brain death was induced by inflation of a subdural balloon catheter. Preload, afterload, and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In Group H (humoral factors), the hearts of healthy dogs were perfused with blood from brain-dead support dogs (n = 6). In Group N (neural factors), the hearts of brain-dead dogs were perfused with blood from healthy support dogs (n = 6). In Group H + N (humoral and neural factors), the hearts of brain-dead dogs were perfused parabiotically in situ with the animals' own blood (n = 6). Systolic and diastolic pressure-volume relationships and coronary blood flow were measured. RESULTS: Induction of brain death led to a significant hyperdynamic response in all groups, with a maximal reaction in Group H + N followed by Group H and Group N. After the initial hyperdynamic phase, cardiac function returned to baseline within 15 minutes and remained stable in all groups for the 2-hour observation period. CONCLUSIONS: (1) Both neural and humoral factors contribute to the initial hyperdynamic reaction after brain death, and only in combination do they cause a maximal hemodynamic effect. (2) If loading conditions and perfusion pressure are kept constant, no cardiac dysfunction occurs after brain death. This indicates that poor cardiac function in the potential donor may reflect altered loading conditions and impaired coronary perfusion rather than neurohumorally mediated direct myocardial injury.

Animals↗
PubMed1996

Effects of milrinone and sulmazole on left ventricular mechanoenergetics in canine hearts.

BACKGROUND: The effect of cardiotonic drugs with calcium-sensitizing effect (Ca2+ sensitizers) on cardiac mechanoenergetics is not fully understood. Accordingly, the effects of milrinone (a phosphodiesterase inhibitor) and sulmazole (a calcium sensitizer with a phosphodiesterase-inhibiting effect) on left ventricular mechanics and energetics were studied. METHODS AND RESULTS: In excised, cross-circulated canine hearts, myocardial oxygen consumption (Vo2), left ventricular contractility index (Emax), and systolic pressure-volume area (a measure of ventricular total mechanical energy) were measured before and during administration of either drug. Milrinone significantly increased Emax by 108.7 +/- 45.9% (mean +/- SD), from 6.3 +/- 3.5 to 13.1 +/- 6.8 mmHg.mL-1.100 g (P < .05), and sulmazole, by 73.6 +/- 54.2%, from 6.3 +/- 2.6 to 10.3 +/- 2.9 mmHg.mL-1.100 g (P < .05). Milrinone significantly abbreviated the contraction duration (Tmax) from 171 +/- 19 ms to 153 +/- 20 ms (P < .05), whereas sulmazole did not (164 +/- 36 ms to 161 +/- 31 ms, not significant), suggesting that the inotropic mechanisms of these two drugs differed. However, both drugs significantly increased the Vo2 intercept of the Vo2/pressure-volume area relation (milrinone: 0.027 +/- 0.004 to 0.036 +/- 0.003 mL O2/beat/100 g, P < .05; sulmazole: 0.025 +/- 0.005 to 0.032 +/- 0.006 mL O2/beat/100 g, P < .05) without significantly changing the slope (reciprocal of contractile efficiency). This parallel upward shift of the Vo2/pressure-volume area relation was similar to that observed with epinephrine and ouabain in our previous studies. CONCLUSIONS: These results suggest that the two positive inotropic drugs exhibit similar mechanoenergetic effects in the normal canine heart despite the different mechanisms of action.

Animals↗
PubMed2001

Artificial liver support devices for fulminant liver failure.

Artificial liver-support devices attempt to bridge patients with fulminant hepatic failure until either a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal function. It is thought that toxins contribute to the clinical picture of fulminant hepatic failure. The earliest reports of successful toxin removal were blood- and plasma-exchange transfusions. Given these successful case reports, mechanical liver-support devices were designed to filter toxins. These mechanical devices used hemodialysis, charcoal hemoperfusion, hemoperfusion through cation-exchange resins, hemodiabsorption, and combinations of all of these techniques as in the MARS liver-support device. Despite promising case reports and small series, no controlled studies of mechanical devices have ever showed a long-term survival benefit. Thus, the removal of presumed toxins seems to be insufficient to support patients with fulminant hepatic failure, and the biologic function of the liver must also be replaced. Attempts at replacing the biologic function have included extracorporeal liver perfusion, cross-circulation, and hepatocyte transplantation. Current technologies have combined mechanical and biologic support systems in hybrid liver-support devices. The mechanical component of these hybrid devices serves both to remove toxins and to create a barrier between the patient's serum and the biologic component of the liver-support device. The biologic component of these hybrid liver support devices may consist of liver slices, granulated liver, or hepatocytes from low-grade tumor cells or porcine hepatocytes. These biologic components are housed within bioreactors. Currently the most clinically studied bioreactors are those that use capillary hollow-fiber systems. Both the bioartificial liver by Demetrious and the extracorporeal liver-assist device by Sussman and Kelly are in clinical trials. Although the trials seemed to have yielded good survival data when the devices are used as a bridge to transplantation, the type and degree of liver support provided by these devices remains uncertain. Thus, despite decades of great progress in the field of artificial liver support, no one technique alone yet provides sufficient liver support. A hybrid system seems to be the best option at present. Still to be determined is the best tissue to use, how much liver tissue should be used, and the optimal design of the bioreactor.

Cell Transplantation↗
PubMed2002

Dissecting tumour pathophysiology using intravital microscopy.

For a systemically administered therapeutic agent to reach neoplastic cells, it must enter the blood circulation, cross the vessel wall, move through the extracellular matrix and avoid getting cleared by the lymphatics. In tumours, each of these barriers is abnormal, changes with space and time, and depends on host-tumour interactions. Intravital microscopy has provided unprecedented molecular, cellular, anatomical and functional insights into these barriers and has revealed new approaches to improved detection and treatment.

Animals↗
PubMed2002

Atrial activation sequence during junctional tachycardia induced by thermal stimulation of Koch's triangle in canine blood-perfused atrioventricular node preparation.

Junctional tachycardia is observed during radiofrequency ablation of the slow pathway. The authors investigated the atrial activation sequence during junctional tachycardia induced with thermal stimulation in canine blood-perfused atrioventricular node (AVN) preparation. The canine heart was isolated (n = 7) and cross-circulated with heparinized arterial blood of the support dog. The activation sequence in the region of Koch's triangle (15 x 21 mm) was determined byrecording 48 unipolar electrograms. Atrial sites anterior to the coronary sinus ostium (site AN), close to the His-potential recording site (site N) and superior to site N (site F), were subjected to a continuous temperature rise from 38 degrees C to 50 degrees C with a heating probe. The temperature of the tissue adjacent to the heating site was monitored simultaneously. Junctional tachycardia at a rate of 92+/-12 beats/min with the His potential preceding the atrial one in the His-bundle electrogram was induced during thermal stimulation at site AN (temperature 42.1 degrees C+/-0.9 degrees C) in all seven preparations, whereas junctional tachycardia was induced during stimulation at site N in one and at site F in none. In each case, the temperature rose only at the site of stimulation. The earliest activation site during junctional tachycardia induced by site AN stimulation was at the His-potential recording site in five preparations and the middle of Koch's triangle in the other two. After creating an obstacle between sites AN and N, atrial tachycardia at a rate of 85+/-11 beats/min was induced during site AN stimulation. The earliest activation site during this tachycardia was site AN. Thus, junctional tachycardia induced by thermal stimulation was suggested to originate from the AN thermal stimulation site. The impulse from the stimulation site appeared to conduct via the posterior input to the compact AVN and junctional tachycardia was generated. When the posterior input was interrupted, atrial tachycardia was generated.

Animals↗
PubMed1995

Extrauterine twin-twin transfusion syndrome after birth in conjoined twins.

Cross-circulation of conjoined twins in utero has been demonstrated and the extent of its severity has varied. Significant 'extrauterine' twin-twin transfusion syndrome after birth, however, caused by an unbalanced shunting within the circulation has not been reported. In a case of omphalopagus conjoined twins complicated by hypovolemia in one twin and hypervolemia in the other, we demonstrated by color Doppler imaging an aberrant vessel from the hepatic artery of one twin to the hepatic vein of the other. Unbalanced shunting through this aberrant vessel was suspected and urgent separation of the conjoined twins was undertaken. Circulatory changes after birth leading to 'extrauterine twin-twin transfusion syndrome' are discussed. A possible explanation of the pathophysiology of intrauterine twin-twin transfusion syndrome is also given.

Adult↗
PubMed2001

Internal carotid artery hemorrhage after irradiation and osteoradionecrosis of the skull base.

OBJECTIVE: To evaluate the clinical presentation and management of internal carotid artery rupture after irradiation and osteoradionecrosis of the skull base. STUDY DESIGN AND SETTING: A retrospective review of the patients in an otorhinolaryngology-head and neck secondary and tertiary referral center. METHODOLOGY: From January 1993 to December 1996, patients with hemorrhage from internal carotid artery as a complication of irradiation and osteoradionecrosis of skull base were reviewed and analyzed. RESULTS: Four patients with internal carotid arterial rupture were included in this study. Angiography was performed in all cases. Embolization of the aneurysm was performed on 2 patients and the remaining 2 patients underwent occlusion of their internal carotid arteries. Three of the 4 patients did not survive. The fourth is currently alive and well 18 months after embolization of 1 internal carotid artery. CONCLUSION: Skull base osteoradionecrosis with bleeding from internal carotid artery is a potentially fatal complication of irradiation. Angiography was the mainstay of diagnosis with embolization of the aneurysm and embolization or ligation of the internal carotid artery being the management options. Internal carotid artery occlusion is the definitive treatment provided cross circulation is adequate. SIGNIFICANCE: The advantages and disadvantages of the treatment options are discussed and a management protocol is proposed.

Aged↗
PubMed1995

Chylomicron metabolism in normal, cholesterol-fed, and Watanabe heritable hyperlipidemic rabbits. Saturation of the sequestration step of the remnant clearance pathway.

The plasma clearance of radiolabeled chylomicrons was compared in normal, cholesterol-fed, and Watanabe heritable hyperlipidemic (WHHL) rabbits. Chylomicron clearance was rapid in normal rabbits but was significantly retarded in cholesterol-fed and WHHL rabbits. At 40 min after the injection of chylomicrons, 14-17% of the injected dose remained in the plasma of normal rabbits, whereas approximately 40-50% of the injected dose remained in the plasma of cholesterol-fed and WHHL rabbits. The differences were reflected in the reduced plasma clearance by the liver and bone marrow of the cholesterol-fed and WHHL rabbits. The hyperlipidemic rabbits expressed normal levels of low density lipoprotein (LDL) receptor-related protein/alpha 2-macroglobulin receptor in the liver. In contrast, the hepatic levels of LDL receptors were lower in hyperlipidemic rabbits; as expected, they were significantly lower in WHHL rabbits compared with normal and cholesterol-fed rabbits. Furthermore, it was demonstrated that lipoproteins accumulating in the plasma of the hyperlipidemic rabbits competed for and retarded the clearance of chylomicrons from the plasma. Competition was demonstrated by cross-circulation of normal and cholesterol-fed or normal and WHHL rabbits, in which the rapid influx of plasma containing the accumulated plasma lipoproteins from cholesterol-fed or WHHL rabbits was shown to impair the uptake of chylomicrons by the liver and bone marrow of normal rabbits. These observations were extended by infusing isolated lipoproteins into normal rabbits. The rabbit d < 1.02 g/ml (remnant) fraction and the canine cholesterol-rich high density lipoproteins (HDL) with apolipoprotein E (HDLc) inhibited chylomicron clearance, whereas human LDL and HDL from humans and rabbits did not. We conclude that the low LDL receptor activity in the cholesterol-fed and WHHL rabbits may contribute, at least in part, to the impaired clearance by decreasing remnant uptake and causing the accumulation of chylomicron and/or very low density lipoprotein remnants. The accumulated remnant lipoproteins then compete for and saturate the mechanism responsible for the initial rapid clearance of chylomicrons from the plasma. We speculate that saturation of the initial rapid clearance may occur at the sequestration step, which involves the binding of remnants to heparan sulfate proteoglycans in the space of Disse.

Animals↗
PubMed1996

The isolation and transplantation of the brain. An historical perspective emphasizing the surgical solutions to the design of these classical models.

Following an historical review of earlier attempts to develop separated head and brain preparations and their contributions to modern-day understanding of the neurophysiology and neurochemistry of the central nervous system, the experiments that eventually led to the first successful total isolation of the mammalian brain are presented. The operative strategies emphasizing the anatomical and physiological problems requiring solution that resulted in vascular and neurogenic separation from the parent body and cephalon are described. The innovative engineering concepts that were utilized in the design of miniaturized equipment to maintain the isolated brain in a living state under conditions of cross circulation, extracorporeal artificial perfusion and transplantation are elaborated. Investigations employing isolated brain and cephalic preparation documenting tissue substrate requirements, metabolic and rheological conditions prevailing at various low temperatures and the immunologically privileged state of the separated organ are briefly presented. The unique opportunities these isolated brain models offer for study are emphasized as well as the complexity of their surgical preparation, which, to date, has limited their universal applications.

Animals↗
PubMed1970

Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis.

Healing skin wounds were studied in a series of parabiotic rats. The femurs of one parabiont of each pair were shielded whilst both animals were given 800 r from a Co(60) source. The animals were wounded 3 days after irradiation. Each animal with partially shielded marrow was then given tritiated thymidine intraperitoneally daily while the cross-circulation was arrested by clamping. After the thymidine-(3)H had cleared the blood, the clamp was released. Animals were sacrificed, and wounds were prepared for radioautography 1, 2, and 6 days after wounding. In the wounds of the shielded animals thymidine-(3)H was observed in epidermis, endothelium, leukocytes, fibroblasts, and mast cells. Only neutrophilic leukocytes, monocytes, and lymphocytes were labeled, as determined by light and electron microscope radioautography, in the wounds of each nonshielded parabiont. None of the many fibroblasts present were found to contain label in the wounds of the nonshielded parabionts through the 6 day period. These observations provide further evidence that wound fibroblasts do not arise from hematogenous precursors and, therefore, must arise from adjacent connective tissue cells.

Animals↗
PubMed1960

Studies in the pathogenesis of experimental dysentery intoxication. Production of lesions by introduction of toxin into the cerebral ventricles.

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion.

Bacillus↗
PubMed1989

Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts.

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.

Action Potentials↗
PubMed1990

Ischaemically induced alterations in electrical activity and mechanical performance of isolated blood perfused canine myocardial preparations.

STUDY OBJECTIVE: The aim was to investigate the direct effect of ischaemic insult on the electrical activity or mechanical performance of the sinoatrial node, atrioventricular node or Purkinje fibres (ventricular papillary muscle) of the dog heart. DESIGN: The three isolated tissues independently mounted in a water jacketed glass container were cross circulated through their respective arteries at a constant pressure (120 mm Hg) with arterial blood from a heparinised supporting dog under sodium pentobarbitone anaesthesia. Rate of automatic rhythmical contractions (automaticity) or tension development was measured before, during, and after ischaemia (30 min). EXPERIMENTAL PREPARATIONS: Seven sinoatrial nodes, five atrioventricular nodes, and 11 papillary muscles were prepared from the heart of mongrel dogs, weighing 11.5-15 kg. MEASUREMENTS AND MAIN RESULTS: The automaticity of the sinoatrial node and atrioventricular node exhibited a high degree of resistance to ischaemia, whereas both the automaticity (Purkinje fibres) and the tension development of papillary muscle were more susceptible to ischaemia and ultimately disappeared during ischaemia. Upon resumption of the blood supply, contractility rapidly returned to preischaemic levels. However, force-frequency analyses revealed that even after reperfusion, papillary muscle had lost the ability to respond normally to stimulus frequencies greater than 2 Hz. CONCLUSIONS: The findings suggest (1) that in the special excitatory and conductive system, the more distal the segment is to the sinoatrial node, the more vulnerable it is to ischaemia; (2) that the myocardium impaired by ischaemic insult lacks functional reserve, as evidenced by enlargement of the differences between the alternate tensions of pulsus alternans; and (3) that cessation of the blood supply does not predominantly damage those tissues whose functions are mainly regulated by a slow inward calcium current.

Animals↗
PubMed1994

Effect of heart rate on myocardial relaxation in isometric twitches.

OBJECTIVE: Increased heart rate increases the amount of calcium that triggers myofilament interaction and thereby the load of calcium to be sequestered to cause relaxation, while decreasing the time for calcium sequestration. By studying the effect of heart rate on myocardial relaxation the hypothesis was therefore tested that increased heart rate impairs myocardial relaxation. METHODS: In situ blood-perfused right ventricular papillary muscles of seven isolated Suga-Sagawa cross circulated canine hearts were studied with a servo system that clamped muscle length to produce isometric force, F(t), at one isometric length in each muscle at paced heart rates within the range 100-150. Each curve of F(t) was fitted, by Marquardt's algorithm, with the relation F(t) = C(t/A)B(e)1-(t/A)B. It was previously shown that the parameter B reflects changes in relaxation, whereas the parameters A and C reflect chronotropic and inotropic states. Changes in B reflect changes in the time course of relaxation that are not simply due to changes in total twitch duration guaranteed to be produced by altered heart rate. Linear regression analysis was performed on data from each muscle to determine whether each of the parameters A, B, and C changed significantly with heart rate. RESULTS: The mean coefficient of determination, a measure of goodness of fit of the model to observed data, was 0.996(SD 0.001). With increase in heart rate, A and C increased significantly in six of the seven muscles. On the other hand B did not show significant change with heart rate in six of the seven muscles; in the seventh muscle, B increased significantly with heart rate. Similar results were obtained when other indices of lusitropy were used. CONCLUSIONS: Increase in heart rate does not impair myocardial lusitropy as measured by the parameter B which reflects changes in the time course of relaxation independent of change in total time course of mechanical activity.

Animals↗
PubMed1994

Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle.

OBJECTIVE: Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. METHODS: The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the Emax (a contractility index)--VO2 (myocardial oxygen consumption)--PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. RESULTS: Pentobarbitone increased Emax at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased Emax dose dependently at high doses in all the hearts and lowered the VO2 intercept but not the slope (oxygen cost of PVA) of the VO2-PVA relation. There was no difference in oxygen cost of Emax between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. CONCLUSIONS: Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts.

Animals↗
PubMed1997

Mechanoenergetics of the negative inotropism of isoflurane in the canine left ventricle. No O2 wasting effect.

BACKGROUND: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2). METHODS: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane. RESULTS: Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). CONCLUSIONS: These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation-contraction coupling without myocardial oxygen wasting effect.

Anesthetics, Inhalation↗