Tribute to Dr. Takuo Aoyagi, inventor of pulse oximetry.

INTRODUCTION: Dr. Takuo Aoyagi invented pulse oximetry in 1974. Pulse oximeters are widely used worldwide, most recently making headlines during the COVID-19 pandemic. Dr. Aoyagi passed away on April 18, 2020, aware of the significance of his invention, but still actively searching for the theory that would take his invention to new heights. METHOD: Many people who knew Dr. Aoyagi, or knew of him and his invention, agreed to participate in this tribute to his work. The authors, from Japan and around the world, represent all aspects of the development of medical devices, including scientists and engineers, clinicians, academics, business people, and clinical practitioners. RESULTS: While the idea of pulse oximetry originated in Japan, device development lagged in Japan due to a lack of business, clinical, and academic interest. Awareness of the importance of anesthesia safety in the US, due to academic foresight and media attention, in combination with excellence in technological innovation, led to widespread use of pulse oximetry around the world. CONCLUSION: Dr. Aoyagi's final wish was to find a theory of pulse oximetry. We hope this tribute to him and his invention will inspire a new generation of scientists, clinicians, and related organizations to secure the foundation of the theory.

Anesthetic management of a patient with aortocaval fistula.

Aortocaval fistula is a rare complication of ruptured abdominal aortic aneurysm (AAA), and patients with an aortocaval fistula show multiple symptoms. We report an 87-year-old man who was diagnosed as having an AAA with aortocaval fistula and who developed refractory hypotension after induction of anesthesia. Following a phenylephrine injection for slight hypotension induced by anesthetic induction, he developed severe hypotension and bradycardia, and his skin became cyanotic. Vasopressor agents had no immediate effect on the hypotension, but blood pressure gradually increased in about 30 min with continuous infusion of dopamine and noradrenaline. Transesophageal echocardiography (TEE) showed right ventricle (RV) hypokinesis and massive tricuspid regurgitation (TR). Central venous pressure (CVP) showed a remarkably high value. After the repair of the aortocaval fistula, the hemodynamics became stable, RV motion was improved, TR was reduced, and CVP became normal. Anesthetic management of the repair of an aortocaval fistula is very difficult. The hemodynamics changed dramatically throughout anesthesia in our patient with this disorder, even though low-dose anesthetics were used. For the successful treatment of this disorder, preparation for the operation is required before the induction of anesthesia, and urgent closure of the fistula is necessary after the induction of anesthesia. TEE is a useful tool for monitoring hemodynamics in such patients.

Plasmin induces endothelium-dependent nitric oxide-mediated relaxation in the porcine coronary artery.

OBJECTIVE: Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation. METHODS AND RESULTS: In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1-activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca2+ concentrations ([Ca2+]i). The preceding stimulation with plasmin inhibited the subsequent [Ca2+]i elevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production. CONCLUSIONS: The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.

Large volume autologous plasma predonation and retransfusion in orthopedic surgical patients.

BACKGROUND: Intraoperative washed autologous transfusion of the scavenged blood can reduce the deterioration of anemia, even during the operation with a comparatively large blood loss. On the other hand, plasma level can not be collected by this system. The preoperative donation and perioperative retransfusion of autologous plasma may reduce the plasma dilution. PURPOSE: The influence of a large volume plasma predonation and perioperative retransfusion on the plasma protein level was investigated. METHODS: Thirteen patients (63.2 +/- 13.2 yr, 70.3 +/- 12.1 kg) were examined regarding their serum protein (SP), IgG, coagulation systems, colloid osmotic pressure (COP), blood cell count before, just after, 2 h after and 7 days after the donation of 900 ml plasma by plasmapheresis with a simultaneous volume replacement. Twenty surgical patients (52.8 +/- 17.3 yr, 72.6 +/- 16.6 kg, the mean predonated autologous plasma: 2100 ml) with intra- and postoperative retransfusion of autologous plasma were examined perioperatively for SP, IgG, coagulation systems and COP. These parameters were compared with that of the predonated plasma. RESULTS: All data including SP, coagulation and COP, with the exception of IgG, completely recovered within 7 days after preoperative plasmapheresis. Perioperatively, autologous washed blood transfusion system was used. The retransfused volume of autologous predonated plasma was 1740 ml on average. Although about 41 of blood on average was lost perioperatively, only one patient out of 20 patients had to be administered homologous red blood cell transfusion. The levels of most parameters, except for COP, constantly recovered in accordance with the autologous plasma transfusion. Differences in the patterns of improvement were also observed between the parameters. CONCLUSION: A 900 ml plasma predonation can therefore be safely performed with an interval of not less than a week between the last donation and the operation. Autologous plasma retransfusion is thus considered to improve the protein levels.

Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization.

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived H2O2 is an EDHF in mesenteric arteries of mice and humans and in porcine coronary microvessels. However, the mechanism for the endothelial production of H2O2 as an EDHF remains to be elucidated. In this study, we tested our hypothesis that Cu,Zn-superoxide dismutase (Cu,Zn-SOD) plays a pivotal role in endothelium-dependent hyperpolarization, using control and Cu,Zn-SOD-/- mice. In mesenteric arteries, EDHF-mediated relaxations and hyperpolarizations were significantly reduced in Cu,Zn-SOD-/- mice with no inhibitory effect of catalase, while endothelium-independent relaxations and hyperpolarizations were preserved. Endothelial H2O2 production also was significantly reduced in Cu,Zn-SOD-/- mice. In Langendorff isolated heart, bradykinin-induced increase in coronary flow was significantly reduced in Cu,Zn-SOD-/- mice, again with no inhibitory effect of catalase. The exogenous SOD mimetic tempol significantly improved EDHF-mediated relaxations and hyperpolarizations and coronary flow response in Cu,Zn-SOD-/- mice. These results prove the novel concept that endothelial Cu,Zn-SOD plays an important role as an "EDHF synthase" in mice, in addition to its classical role to scavenge superoxide anions.

[Anesthesia for a patient with xeroderma pigmentosum].

A 23-year-old man with xeroderma pigmentosum underwent laparoscopic cholecystectomy. He experienced transient worsening of the neurological symptom after anesthesia with volatile agents in the previous surgery. Because volatile anesthetics potentially cause genotoxic effects in patients with xeroderma pigmentosum, this time we chose total ir.travenous anesthesia (TIVA). The intraoperative management and the post-operative course were uneventful this time. From these two anesthesia experiences in one patient, we suggest that TIVA is more appropriate than anesthesia with volatile agents as a method for general anesthesia for xeroderma pigmentosum patients. Minimum usage of muscle relaxants under the monitoring of neuromuscular blockade is also recommended, since xeroderma pigmentosum patients are sensitive to muscle relaxants due to the neuronal dysfunction and muscle

Prognosis of patient with cardiopulmonary arrest transported to Kyushu University Hospital.

Three hundreds and sixty six patients with out-of-hospital cardiopulmonary arrest, transported to the Kyushu University Hospital from 2000 to 2006, were examined using the Utstein style in witnessed cardiogenic cardiopulmonary arrest patients. Also, we examined the influence on prognosis due to the difference in the treatment of airway control in out-of-hospital settings. Nineteen patients out of 78 witnessed cardiogenic out-of-hospital cardiopulmonary arrest patients were discharged alive and 11 were with a good prognosis. The number of cases where an initial electrocardiographic complex showed ventricular fibrillation or pulseless ventricular tachycardia was higher than formerly reported in Japan and was equal to the incidence reported in Europe and America. In addition, the survival discharge rate of patients with the ventricular fibrillation or pulseless ventricular tachycardia was higher than that previously reported in Japan and was similar to European and American results. Manual airway maintenance using a bag valve mask was more successful in terms of the survival discharge rate compared to the use of advanced airway devices. By the time course, collapse to cardiopulmonary resuscitation interval, collapse to initial defibrillation interval and collapse to the return of spontaneous circulation interval were shorter in the group discharged with a good prognosis, especially in the witnessed ventricular fibrillation or pulseless ventricular tachycardia patients corresponding to former reports. Most patients with a good prognosis resuscitated before arrival at the hospital. These results suggest the prehospital treatment is the critical point other than in-hospital treatment.

Rapid and random turnover of mitochondrial DNA in rat hepatocytes of primary culture.

It is known that mitochondrial DNA (mtDNA) replication is independent of the cell cycle. Even in post-mitotic cells in which nuclear DNA replication has ceased, mtDNA is believed to still be replicating. Here, we investigated the turnover rate of mtDNA in primary rat hepatocytes, which are quiescent cells. Southwestern blot analysis using 5-bromo-2'-deoxyuridine (BrdU) was employed to estimate the activity of full-length mtDNA replication and to determine efficient doses of replication inhibitors. Southern blot analysis showed that a two-day treatment with 20mM 2',3'-dideoxycytidine and 0.2mug/ml ethidium bromide caused a 37% reduction in the amount of mtDNA, indicating that the hepatocytes had a considerably high rate of turnover of mtDNA. Further, pulse-chase analysis using Southwestern analysis showed that the amount of newly synthesized mtDNA labeled with BrdU declined to 60% of the basal level within two days. Because the rate of reduction of the new mtDNA was very similar to the overall turnover rate described above, it appears that degrading mtDNA molecules were randomly chosen. Thus, we demonstrated that there is highly active and random turnover of mtDNA in hepatocytes.

Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system.

Intracellular signaling pathway mediated by small GTPase Rho and its effector Rho-kinase plays an important role in regulation of vascular smooth muscle contraction and other cellular functions. We have recently demonstrated that Rho-kinase is substantially involved in angiotensin II-induced gene expressions and various cellular responses in vitro. However, it remains to be examined whether Rho-kinase is involved in the angiotensin II-induced cardiovascular hypertrophy in vivo and, if so, what mechanisms are involved. Long-term infusion of angiotensin II for 4 weeks caused hypertrophic changes of vascular smooth muscle and cardiomyocytes in rats. Both changes were significantly suppressed by concomitant oral treatment with fasudil, which is metabolized to a specific Rho-kinase inhibitor, hydroxyfasudil, after oral administration. Angiotensin II caused a perivascular accumulation of macrophages and Rho-kinase activation, both of which were also significantly suppressed by fasudil. Vascular NAD(P)H oxidase expression (nox1, nox4, gp91phox, and p22phox) and endothelial production of superoxide anions were markedly increased by angiotensin II, both of which were also significantly suppressed by fasudil. Thus, fasudil ameliorated the impaired endothelium-dependent relaxations caused by angiotensin II without affecting vasodilator function of vascular smooth muscle. These results provide evidence that Rho-kinase is substantially involved in the angiotensin II-induced cardiovascular hypertrophy in rats in vivo. The suppression of endothelial NAD(P)H oxidase upregulation and resultant superoxide production and the amelioration of endothelial vasodilator function may be involved in this process.

[Dexmedetomidine].

Dexmedetomidine, a potent and highly selective alpha2-agonist, provides a unique "conscious sedation" (patients appear to be asleep, but are readily roused), analgesia, without respiratory depression. In order to provide a comfortable sedation to the ICU patients, careful evaluation of sedation and analgesia level, and the consistent treatment by medical teams are necessary. We may expect the usefulness of dexmedetomidine in the settings other than the ICU, from its pharmacological properties. Clinical applications of dexmedetomidine for several procedures such as awake craniotomy, fiberoptic tracheal intubation, or MRI examination have been reported, suggesting its usefulness and problems. The major problem with dexmedetomidine is its hemodynamic effects. Because this drug often causes hypotension, hypertension and bradycardia, it should be used under the control by skilled medical teams.

Transduction of the N-terminal fragments of MYPT1 enhances myofilament Ca2+ sensitivity in an intact coronary artery.

OBJECTIVE: The region of the 110 kDa regulatory subunit (MYPT1) of smooth muscle myosin phosphatase involved in the regulation of contraction was determined under physiological conditions. METHODS AND RESULTS: Using HIV Tat protein-mediated protein transduction, the N-terminal fragments of MYPT1 were introduced to the intact porcine coronary arterial strips. Pre-incubation with 3 micromol/L TAT-MYPT1(1-374), a construct containing the Tat peptide and the residues 1 to 374 of MYPT1, for 15 minutes augmented (2.4-fold) the subsequent contraction induced by adding 1.25 mmol/L of extracellular Ca2+ under 118 mmol/L K+ depolarization, with no augmentation of the [Ca2+]i elevation. The deletion of the Tat peptide, MYPT1(1-374), abolished the augmenting effect. TAT-MYPT1(1-296) demonstrated a weaker but significant augmentation (1.7-fold). However, TAT-MYPT1(1-171), TAT-MYPT1(39-374), TAT-MYPT1(39-296), and TAT-MYPT1(297-374) had no augmenting activity. The myosin light chain phosphorylation level as a function of extracellular Ca2+ concentrations was shifted to the left in the strips pretreated with TAT-MYPT1(1-374) compared with the control. CONCLUSIONS: Region 1 to 296 was the minimal region involved in the enhancement of contraction, and region 297 to 374 played a supplemental role. These results suggested that the interaction mainly between catalytic subunit and MYPT1 play a critical role in the regulation of the endogenous myosin phosphatase in intact smooth muscle.

Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm.

OBJECTIVE: We have recently demonstrated that protein kinase C (PKC) and Rho-kinase play important roles in coronary vasospasm in a porcine model. However, it remains to be examined whether there is an interaction between the two molecules to cause the spasm. METHODS AND RESULTS: A segment of left porcine coronary artery was chronically treated with IL-1beta-bound microbeads in vivo. Two weeks after the operation, phorbol ester caused coronary spasm in vivo and coronary hypercontractions in vitro at the IL-1beta-treated segment; both were significantly inhibited by hydroxyfasudil, a specific Rho-kinase inhibitor. Guanosine 5'-[gamma-thio]triphosphate (GTPgammaS), which activates Rho with a resultant activation of Rho-kinase, enhanced Ca2+ sensitization of permeabilized vascular smooth muscle cells, which were resistant to the blockade of PKC by calphostin C. The GTPgammaS-induced Ca2+ sensitization was greater in the spastic segment than in the control segment. Western blot analysis revealed that only PKCdelta isoform was activated during the hypercontraction. CONCLUSIONS: These results demonstrate that PKC and Rho-kinase coexist on the same intracellular signaling pathway, with PKC located upstream on Rho-kinase, and that among the PKC isoforms, only PKCdelta may be involved. Thus, the strategy to inhibit Rho-kinase rather than PKC may be a more specific and useful treatment for coronary spasm.

Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries.

Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases. We have recently demonstrated that Rho-kinase plays a key role in the spasm in our porcine model. However, it remains to be elucidated whether Rho-kinase-mediated pathway also contributes to vasoconstriction of human arteries. From 15 patients who underwent coronary artery bypass operation, segments of isolated left internal thoracic arteries were obtained, and the endothelium was gently removed. Serotonin and histamine caused contractions, which were markedly inhibited by a specific Rho-kinase inhibitor, hydroxyfasudil. Western blot analysis showed that, during the serotonin-induced contractions, the extent of phosphorylation of myosin-binding subunit of myosin phosphatase (MBS, one of the major substrates of Rho-kinase) was significantly increased in the specimens. Hydroxyfasudil again significantly suppressed the serotonin-induced increase in MBS phosphorylation. There was a significant positive correlation between the extent of MBS phosphorylation and that of the serotonin-induced contractions and between hydroxyfasudil-sensitive components of the contractions and the extent of arteriosclerosis. These results indicate that Rho-kinase plays an important role in vascular smooth muscle contractions of arteriosclerotic human arteries, suggesting that Rho-kinase could be regarded as an important target for the treatment of arteriosclerotic vascular diseases in humans.

Propofol prevents endothelial dysfunction induced by glucose overload.

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. 2 D-glucose overload (23 mM) induced an accumulation of superoxide anion (O2-), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 microU ml(-1) xanthine oxidase (XO) and 100 micro M xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 micro M, whereas much higher concentrations of propofol were required to scavenge O2- generated by 250 microU ml(-1) XO and 100 microM xanthine (IC50: 13.5 micro M). 3 D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC50 of 0.60 microM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 microM). 4 D-glucose overload suppressed ATP-induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2- was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 microM, respectively. 5 D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 micro M propofol reduced this increase to 2.8 fold. 6 We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2- accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.

Unproductive cleavage and the inactivation of protease-activated receptor-1 by trypsin in vascular endothelial cells.

1 Using fura-2 fluorometry of [Ca(2+)](i) in response to thrombin, trypsin and protease-activated receptor activating peptides (PAR-APs), we determined whether trypsin cleaves protease-activated receptor 1 (PAR1) and activates it in the endothelial cells of the porcine aortic valves and human umbilical vein. 2 Once stimulated with thrombin, the subsequent application of trypsin induced a [Ca(2+)](i) elevation similar to that obtained without the preceding stimulation with thrombin in the valvular endothelial cells. However, the preceding stimulation with trypsin abolished the subsequent response to thrombin, but not to bradykinin or substance P. 3 The response to PAR1-AP (SFLLRNP) was significantly (P<0.05) reduced by the preceding stimulation with thrombin and PAR1-AP in the valvular endothelial cells, while, importantly, it remained unaffected by the preceding stimulation with either trypsin or PAR2-AP (SLIGRL). The response to PAR2-AP was reduced by the preceding stimulation with trypsin and PAP2-AP. PAR1-AP attenuated the subsequent responses not only to thrombin and PAR1-AP but also to trypsin and PAR2-AP, while PAR2-AP specifically attenuated the subsequent responses to trypsin and PAR2-AP. 4 In human umbilical vein endothelial cells, a higher affinity PAR1-AP (haPAR1-AP) (Ala-pF-Arg-Cha-HArg-Tyr-NH(2)) specifically attenuated the responses to thrombin but not trypsin. On the other hand, the response to haPAR1-AP was significantly (P<0.05) attenuated by the preceding stimulation with thrombin but not trypsin. 5 In conclusion, trypsin cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the trypsin-cleaved PAR1 was no longer responsive to thrombin.

Inactivation of protease-activated receptor-1 by proteolytic removal of the ligand region in vascular endothelial cells.

Proteolysis plays an important role in inactivating protease-activated receptor-1 (PAR1). We aimed to determine the cleavage site(s) responsive for the proteolytic inactivation of PAR1 in human umbilical vein endothelial cells. Fura-2 fluorometry revealed that the preceding stimulation with trypsin abolished the subsequent [Ca(2+)](i) response to thrombin, while the responses to PAR1-activating peptides remained intact. On the other hand, thrombin had no effect on the subsequent response to trypsin. The immunostaining with antibodies against the residues 35-46 (SPAN12) and 51-64 (WEDE15) revealed the broad boundaries of cleavage. Trypsin removed both epitopes from the cell surface within 3 min, while thrombin removed the epitope of SPAN12. The longer incubation with thrombin removed the epitope of WEDE15. However, PAR1-activating peptides thereafter induced an attenuated but significant elevation of [Ca(2+)](i). Not only the receptor internalization as observed with a confocal microscope, but also an additional cleavage was thus suggested to contribute to the thrombin-induced removal of the epitope of WEDE15. The analyses of the PAR1 mutants identified three cleavage sites for trypsin; residues 41-42, 70-71 and 82-83. The cleavage at the latter two sites was suggested to dominate that at the former, and thus remove the ligand region (residues 42-47). The inactivation of PAR1 due to proteolytic removal of the ligand region may contribute not only to the inactivation of PAR1 by proteases such as trypsin, but also to the termination of the intracellular signaling initiated by thrombin in the vascular endothelial cells.

Persistent hypertension does not alter the cerebral blood flow and glucose utilization in young-adult Dahl salt-sensitive rats.

The Dahl- Iwai salt-sensitive (DS) rat develops hypertension due to a high-salt diet without any structural alterations of the brain arteries and arterioles. We investigated the effect of persistent hypertension on the regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) in the DS rats. The rats were fed either a high-salt diet (HSD; 8% NaCl, n = 5) or a low-salt diet (LSD; 0.3% NaCl, n = 6) from 8 to 16 weeks of age, and the HSD group developed hypertension lasting for 1 month. At 16 weeks of age, the rCBF was measured in the sensorimotor and visual cortices using the hydrogen clearance method, and the rCGU was measured in 26 different brain structures using the [(14)C]deoxyglucose method. The mean arterial pressure was significantly higher in the HSD group (168+/-7 mm Hg) than in the LSD group (139+/-3 mm Hg) (P < 0.01). The mean rCBF and the rCGU values tended to be lower in the HSD group than in the LSD group; however, there were no statistically significant differences except for the reduced rCGU value in the nucleus accumbens. These results suggest that hypertension itself does not alter either the rCBF or the rCGU in young-adult DS rats. This indicates that the functional / structural changes of the cerebral arteries and arterioles that are associated with hypertension appear to be responsible for altered rCBF and rCGU in other animal models of hypertension.

The effects of isoflurane and sevoflurane on the left ventricular end-systolic pressure-volume relation in dogs.

The influence of two inhalational anesthetics, isoflurane and sevoflurane, on the end-systolic pressure-volume relations (ESPVR) of the left ventricle (LV) in situ was investigated in open-chest dogs anesthetized with α-chloralose. The LV volume was measured by a conductance catheter while the LV pressure was measured by a tipmicromanometer. The end-systolic elastance (Ees) of the LV was calculated as the slope of ESPVR which was elicited when the inferior vena cava was transiently occluded. The dogs were randomly assigned to two groups, receiving either 1.3% and 2.6% isoflurane (n=6) or 2.3% and 4.6% sevoflurane (n=6), which are equivalent to 1 and 2 MAC of isoflurane or sevoflurane, respectively. Both isoflurane and sevoflurane produced dose-dependent decreases in the cardiac output to a similar degree. Isoflurane and sevoflurane caused equivalent decreases in Ees of 23% and 16% at 1 MAC, and 48% and 41% at 2 MAC, respectively. Dobutamine 3 µg·kg-1·min-1 produced a simultaneous restoration of Ees and recovery of the cardiac output at 1 and 2 MAC of both isoflurane and sevoflurane. We thus conclude that the depressant effect of sevoflurane on cardiac contractility is almost identical to that of isoflurane in the dog, and they are both reversed by the use of a low dose of dobutamine.

Protamine relaxes vascular smooth muscle by directly reducing cytosolic free calcium concentrations in small resistance arteries.

Protamine has been suggested to relax vascular smooth muscle by reducing the intracellular Ca2+ concentration ([Ca2+]i). However, there has been no direct evidence that protamine reduces the [Ca2+]i of vascular smooth muscle. We therefore studied the effects of protamine on changes in [Ca2+]i and tension induced by norepinephrine (NE) and high K+ in endothelium-denuded strips from rabbit small mesenteric artery, using fura-2-fluorometry and isometric tension recording methods. Both NE (1 µM) and high K+ (40 mM) produced a transient phasic increase, followed by a tonic increase in [Ca2+]i and tension. Protamine concentration (15-500 µg·ml-1)-dependently inhibited (P<0.05) the phasic and tonic components of both NE- and high K+-induced contraction with IC50 values of ≈50 µg·ml-1. Protamine (50 µg·ml-1) inhibited (P<0.05) the phasic and tonic increases in [Ca2+]i caused by both NE and high K+ by ≈40%-60%. We conclude that the direct vasodilator action of protamine is due, at least in part, to reduction of [Ca2+]i in vascular smooth muscle; this reduction in [Ca2+]i may be due to inhibition of both Ca2+ influx and Ca2+ release from intracellular Ca2+ stores.

[Acute renal failure in an infant attributable to arterial cannula malposition during cardiopulmonary bypass via ministernotomy].

A 6-month-old female (4.9 kg) with multiple congenital heart lesions underwent intracardiac repair with the aid of cardiopulmonary bypass (CPB) through a lower half sternotomy. Aortic cannulation, venous cannulation, and cardioplegia cannula insertion were all accomplished through the ministernotomy. During the CPB, in spite of a high perfusion flow rate (182 ml.kg-1.min-1), the systemic arterial pressure was persistently low (mean values = 25-35 mmHg) and the urine output was greatly reduced (< 1 ml.hr-1). In addition, inappropriate increases in the arterial inflow line pressure were recognized. Since abutment of the cannula tip against the aortic intima was suspected, several attempts were made to correct its malpositioning. During the CPB, hemolysis was also found in the mixed venous blood. Since the oliguria and resultant hyperkalemia persisted after weaning from the CPB, peritoneal dialysis was introduced immediately after the surgery. Her renal function gradually recovered postoperatively, and she was finally weaned from the peritoneal dialysis on the 13th postoperative day. Although the ministernotomy has been proposed to be a safe approach for most of cardiac surgeries, it appears to increase the risk for arterial cannula malposition as compared to the standard full-length sternotomy in small pediatric patients.