Biomedical subjects

A Saeki

Publications and source records attributed to A Saeki.

At least 19 recordsLinked to original sources

PubMed1996

Adverse influence of systemic vascular stiffening on cardiac dysfunction and adaptation to acute coronary occlusion.

BACKGROUND: [corrected] Age is an independent risk factor for increased mortality from ischemic heart disease. Arterial stiffening with widening of the pulse pressure may contribute to this risk by exacerbating cardiac dysfunction after total coronary artery occlusion. METHODS AND RESULTS: To test the above hypothesis, 14 open-chest dogs underwent surgery in which the intrathoracic aorta was bypassed with a stiff plastic tube. Directing ventricular outflow through the bypass widened the arterial pulse pressure from 41 to 115 mm Hg at similar mean pressure and flow. Hearts ejecting into the native aorta (NA) exhibited only modest dysfunction after two minutes of mid-left anterior descending coronary artery occlusion. However, the same occlusion applied during ejection into the bypass tube (BT) induced far more severe cardiodepression (ie, systolic pressure fell by -41+/-10 mm Hg for BT versus -15+/-3 mm Hg for NA, and end-systolic volume rose by 15+/-3 versus 6+/-2 mL), with a threefold greater decline in ejection fraction. This disparity was not due to higher baseline work loads because total pressure-volume area was similar in both cases. Furthermore, marked increases in basal work load and wall stress induced by angiotensin II infusion (in four additional studies) did not reproduce this behavior. Although peak systolic chamber stress was greater with the BT, this did not increase systolic dyskinesis as measured in the central ischemic zone. However, the total mass of myocardium that was rendered severely ischemic (ie, flow reduced by > or = 80%) was twice as large with BT ejection, likely expanding the region of dyskinesis. This disparity may relate to altered phasic coronary flow during BT ejection, which displays marked enhancement of systolic flow and renders the heart more vulnerable to diminished mean and systolic perfusion pressures. CONCLUSIONS: Cardiac ejection into a stiff systemic vasculature augments cardiac dysfunction and ischemia due to coronary occlusion by tightening the link between cardiac systolic performance and myocardial perfusion. This may contribute to the higher mortality risk from ischemic heart disease due to age.

Acute Disease↗

PubMed1996

Mechanoenergetics of negative inotropism of ventricular wall vibration in dog heart.

Mechanical vibration depresses cardiac contractility. We studied the mechanoenergetic effects of this negative inotropism in the left ventricle (LV) of an isolated, cross-circulated dog heart preparation. We took full advantage of the mechanoenergetic relationship among the LV end-systolic elastance (Emax, contractility index), systolic pressure-volume area (PVA), and myocardial oxygen consumption (VO2). PVA is a measure of the total mechanical energy that cardiac contraction generates. PVA correlates closely with VO2. The VO2 intercept of the VO2-PVA relation reflects the VO2 component for excitation-contraction (E-C) coupling plus basal metabolism (PVA-independent VO2). VO2 above the PVA-independent VO2 reflects the VO2 component for mechanical contraction (PVA-dependent VO2). When we applied 70-Hz vibration of 2-mm amplitude to a LV wall region, it instantly decreased Emax and PVA by 20%, followed by a 10% decrease in VO2 at a fixed volume. However, the vibration neither lowered the VO2-PVA relation obtained at different LV volumes, unlike ordinary negative inotropism, nor changed its slope (1.88 +/- 0.23 vs. 1.86 +/- 0.23 x 10(-5) ml O2.mmHg-1.ml-1). The virtually zero delta PVA-independent VO2/delta Emax with vibration indicates a much smaller O2 cost of Emax than that seen with calcium and propranolol inotropism. These mechanoenergetics support the hypothesis that mechanical vibration primarily suppresses cardiac contractility without suppressing E-C coupling.

Animals↗

PubMed1996

[Diagnosis of pulmonary aspergillosis in cases with cavity as sequela of tuberculosis].

Non-invasive pulmonary aspergillosis is frequently seen in cases with cavity as sequela of tuberculosis. Diagnosis of non-invasive pulmonary aspergillosis is not easy except for cases whose chest X-ray findings show a typical fungus ball. How to diagnose pulmonary aspergillosis was studied in 21 patients who showed changes in the radiological findings of cavity as sequela of tuberculosis. We made sputum culture of Aspergillus, measurement of precipitin antibody titer to Aspergillus fumigatus and measurement of PASTOREX ASPERGILLUS in serum and sputum on the 21 patients (group A). PASTOREX ASPERGILLUS in sputum was evaluated in three grades: 1+ approximately 3+. We diagnosed 14 patients as pulmonary aspergillosis (PA group) among the 21 patients taking into account the chest X-ray findings and the results of the above-stated investigations. The types of chest X-ray findings of these 14 patients were fungus ball type (FB) in 2 patients, productive aspergilloma on the inner wall of a cavity (PAIC) in 8, mixed type with FB and PAIC in 2 and non-specific change in 2. However, there were 3 patients with the chest X-ray findings suggestive of PAIC in 7 patients (non-PA group) who were not diagnosed as pulmonary aspergillosis. Sputum culture were positive in 11 patients of PA group (79%) and negative in all patients of non-PA group. Precipitin antibody were positive in 8 patients of PA group (67%) and negative in all patients of non-PA group. PASTOREX ASPERGILLUS in serum were negative in all 21 patients. PASTOREX ASPERGILLUS in sputum were 3+ (+3) in all 14 patients of PA group and in 2 patients of non-PA group and 2+ (+2) in 2 patients of non-PA group. 12 patients of PA group were treated by antifungal agents and 11 patients responded well to the treatment. We also made sputum culture of Aspergillus and measurement of PASTOREX ASPERGILLUS in sputum on 14 patients (group B) who had respiratory diseases with stable cavities and 17 patients (group C) who had respiratory diseases without a cavity. In group B, sputum culture were positive in 1 patient and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 2 patients, 2+ (+2) in 1 and 1+ (+) in 2. In group C, sputum culture were negative in all patients and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 1 patient, 2+ (+2) in 3 and 1+ (+) in 2. Measurement of PASTOREX in sputum was a useful tool to diagnose non-invasive aspergillosis in addition to sputum culture and measurement of precipitin antibody titer. The sensitivity of PASTOREX in sputum was high but its specificity was low, however, its specificity could be raised by applying semi-quantitative analysis of PASTOREX in sputum.

Adult↗

PubMed1995

Prevalence of macro- and microvascular diseases in non-insulin-dependent diabetic and borderline glucose-intolerant subjects with insulin resistance syndrome.

This study was undertaken to ascertain whether patients with insulin resistance syndrome, a cluster of risk factors for coronary artery disease (CAD), are really a high risk population for macro- and microvascular diseases in Japanese NIDDM and borderline glucose-intolerant subjects. A diagnosis of insulin resistance syndrome was made if four of the six following criteria are satisfied: glucose disposal rate < 2.2 mg/kg/min, fasting plasma IRI > 15 microU/ml or peak plasma IRI > 100 microU/ml during meal tolerance test, plasma triglyceride > 150 mg/dl at fasting or > 200 mg/dl after meal, serum HDL-cholesterol < 40 mg/dl, blood pressure > 140 mm Hg systolic and > 90 mm Hg diastolic or treatment with antihypertensive agents, and body mass index (BMI) > 27 for men or > 25 for women. We compared the prevalence of CAD, cerebral vascular disease (CVD), peripheral vascular disease (PVD), retinopathy and nephropathy between the insulin resistance syndrome group (group A, n = 57) and the remaining group (group B, n = 164). Both groups did not differ with respect to age, duration of diabetes, BMI, fasting plasma glucose, HbA1c, composition of NIDDM and borderline glucose-intolerance (BGI) or treatment modality. The prevalence of CAD was significantly higher in group A compared with that in group B (31.6% vs. 14.0%, P < 0.002), but not for CVD (8.8% vs. 3.7%, respectively, P = 0.12) or PVD (1.8% vs. 2.4%, respectively, P = 0.76). The prevalence of late-stage retinopathy in group A was significantly higher than that in group B (12.3% vs. 2.4%, respectively, P < 0.005). Macroalbuminuria, but not microalbuminuria, was significantly higher in group A than that in group B (12.3% vs. 3.6%, P < 0.02). We conclude that the insulin resistance syndrome preferentially increases the development of CAD, and is also involved in the progression of microvascular diseases.

Adult↗

PubMed1995

The relationship between insulin resistance and insulin secretion in Japanese subjects with borderline glucose intolerance.

Insulin resistance and impaired insulin secretion can be involved in the development of non-insulin-dependent diabetes mellitus (NIDDM), but their relative importance or temporal relationship are poorly understood. To elucidate this issue, we studied 51 subjects with borderline glucose intolerance (BGI) and 18 normal glucose tolerant subjects (NGT) according to the Japan Diabetes Society criteria. The glucose infusion rate (GIR, mg/kg/min), an index of whole body insulin resistance (IR), was measured by the euglycemic (80 mg/dl) hyperinsulinemic clamp technique (insulin infusion rate 1.12 mU/kg/min). Insulinogenic index (delta IRI/delta BS at 30 min) and the insulin area under the curve during a 75-g oral glucose tolerance test (OGTT) were estimated. In the BGI subjects, the GIR values showed marked variation ranging from 2.24 to 10.44 mg/kg/min (5.54 +/- 0.31, mean +/- S.E.M.). The GIR values were lower in obese BGI subjects compared with non-obese BGI and NGT subjects, and the insulin area was markedly higher in BGI subjects with increased insulin resistance. There was a significant negative correlation between the GIR values and the insulin area or delta IRI/delta BS (30') ratio in the subjects with BGI either in the whole group or solely in the non-obese group. We conclude that the increased insulin secretion compensates for the peripheral insulin resistance of subjects with slightly deteriorated glucose tolerance, implying that insulin resistance plays an important role in the pathogenesis of NIDDM in some fraction of Japanese population.

Adolescent↗

PubMed1995

Metabolic regulation and microangiopathy in a cohort of Japanese IDDM-patients.

In Caucasian patients with insulin-dependent diabetes mellitus (IDDM) proliferative diabetic retinopathy (PDR) and persistent proteinuria (PP) are associated, and major risk factors for development of microangiopathy have been identified. The aim of the present study was to evaluate whether these risk factors are also relevant and whether an association exists between the microangiopathic complications in Japanese IDDM-patients. A clinic-based cohort of 324 Japanese IDDM-patients was followed (a mean follow-up of 7 years). Annual examination for development of PDR and PP was performed. Fifty-eight patients developed PDR and 24 developed PP. Development of PDR was associated to high HbA1c-levels, i.e., the 4th quartile (RR 7.9, P < 0.0001), background retinopathy at admission (RR 9.9, P < 0.0001), high age at diabetes onset (RR 2.9, P < 0.0001) and female gender (RR 1.7, P < 0.05). Development of PP was associated to high HbA1c-levels (RR 2.8, P < 0.001) and background background retinopathy at admission (RR 7.9, P < 0.0001). The risk of developing PP was 9 times higher in patients developing PDR than in patients not developing PDR (P < 0.0001). The effect of metabolic control in our cohort was similar to that found in the DCCT and SDIS studies. In conclusion, development of PP is closely associated with PDR, also in Japanese IDDM-patients. The effect of metabolic control is the same as in Caucasian patients. Development of malignant angiopathy in IDDM-patients is not confined to Caucasian IDDM-patients, and the incidence rates are comparable to those found in Caucasian IDDM.

Adolescent↗

PubMed1995

Cardiac quick-release contraction mechanoenergetics analysis using a cardiac muscle cross-bridge model.

Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components was simulated to examine the conflicting reports on the amount of energy saved by quick release at the peak contraction time. Cross-bridge energy utilization was determined by considering the ATP hydrolysis for the cross-bridge cycling. The quick-release cases were simulated by letting the muscle fiber suddenly shorten to the resting fiber length at peak systole, and then the contraction was allowed to continue at the resting length. Simulation results demonstrated that, using realistic parameter values, typically approximately 15% of the muscle fiber energy is used after peak systole (and approximately 30% of the cross-bridge energy), but this is also a function of the muscle fiber properties characterized by cross-bridge association and dissociation rate constants. Increasing the kinetic rate constants, the series elasticity, the initial fiber length, or the time of peak intracellular calcium will increase the amount of energy left, which may explain some of the discrepancies in the literature. Cardiac muscle hypertrophy will increase the fraction of muscle fiber energy left after peak systole to approximately 30%. The strongest indicator of the percent energy left at peak systole was the time the fiber reached peak systole, and as the fiber reached peak systole faster, the amount of energy saved by quick release increased.

Animals↗

PubMed1995

Newly discovered familial juvenile gouty nephropathy in a Japanese family.

Our attention was initially called to 2 young Japanese sisters with gout and renal insufficiency, which led to an investigation of members of their family with similar conditions. One sister, a 26-year-old woman who had suffered from polyuria since infancy, suffered from gout and renal insufficiency. Her younger sister also had a history of polyuria, hyperuricemia, and moderately reduced renal function. Their urinary uric acid levels were reduced but purine enzyme activities in the erythrocytes were normal. A renal biopsy specimen from the younger sister showed severe interstitial fibrosis with tubular atrophy. An investigation of the family revealed an autosomal dominant transmission pattern. We believe these are new familial cases of juvenile gouty nephropathy found in a Japanese family.

Adult↗

PubMed1995

systolic flow augmentation in hearts ejecting into a model of stiff aging vasculature. Influence on myocardial perfusion-demand balance.

Age-related arterial stiffening and widening of the pulse pressure elevates ventricular systolic wall stress while it lowers diastolic coronary perfusion pressure. These changes are thought to adversely alter the balance between myocardial work load and blood supply. To test this hypothesis, the native compliant thoracic aorta was surgically bypassed by a stiff tube in reflex-blocked anesthetized dogs. Ventricular outflow was directed into either native aorta or the bypass; the latter resulting in an increase in arterial pulse pressure from 37.8 to 107.5 mm Hg (P < .001), with minimal change in mean pressure and flow. Cardiac work load was assessed by pressure-volume area (PVA), which combines external and internal left ventricular work and is linearly related to myocardial oxygen consumption (MVO2), and by MVO2 itself. Regional phasic and mean coronary flow were measured in the left anterior descending coronary artery, and global flow was assessed by radiolabeled microspheres. Myocardial supply-demand balance was assessed by comparing flow at matched PVA or MVO2, flow-PVA relations, and endocardial-to-epicardial flow ratios. When blood flow was directed into the stiff bypass tube, peak systolic pressure, wall stress, and PVA all rose nearly 50%, yet diastolic perfusion pressure fell by 20 mm Hg (all P < .01). Rather than being compromised, however, mean coronary flow rose by 34%, maintaining the same endocardial-to-epicardial flow ratio (approximately 1.1). Flow augmentation persisted when data were compared at matched work load (PVA or MVO2), and mean arterial pressure, as well as over a range of work loads (P < .001 from ANCOVA of flow-PVA relations). The increased flow resulted from enhanced systolic perfusion, which nearly equaled diastolic flow when ejection passed into the stiff bypass. These data counter the notion that cardiac coupling with a stiff arterial system (as with aging) necessarily compromises myocardial flow versus metabolic demand. However, the data highlight a greater role of systolic flow under such conditions and also raise the novel suggestion that enhanced pulsatility of the arterial pressure waveform may itself augment coronary perfusion.

Aging↗

PubMed1995

Insulin sensitivity and negative insulin feedback after pancreas transplantation in insulin-dependent diabetic patients.

The aims of this study were to determine the change in the rate of insulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreas-kidney transplant recipients with insulin-dependent diabetes mellitus. Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation. The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression. Physiological hyperinsulinemia (50-70 microU/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Taking into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subjects and evidence of increased insulin secretion in pancreas recipients, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pancreas in the absence of insulin resistance.

Adult↗

PubMed1995

[RAEB in T with monosomy 7 after treatment of severe aplastic anemia with long term G-CSF].

A 19-year-old male who suffered from severe aplastic anemia had been treated with granulocyte colony stimulating factor (G-CSF) from September 1991. Marked increase of hematopoietic cells in his bone marrow was observed, and maintenance administration of G-CSF was continued. 15 months later, myeloblasts with nuclear abnormality increased, and 22 months later, myeloblasts with chromosomal abnormality presenting 46, XY, -7, +21 exceeded 20%, and aplastic anemia seemed to be transformed into refractory anemia with excess of blasts in transformation (RAEB in T). The usefulness of G-CSF in the treatment of aplastic anemia is now established, but there are some reports questioning the effect of long-term administration, especially transformation to MDS with monosomy 7. Leukemic transformation from aplastic anemia is very complex, but in some cases, long term administration of G-CSF may affect the natural course and may lead to the earlier development of leukemia.

Adult↗

PubMed1995

[Acute myelomonocytic leukemia complicated with syndrome of inappropriate secretion of antidiuretic hormone, nephrotic syndrome, and hemophagocytic syndrome].

A 59-year-old man was admitted to our hospital because of fever in August 1991. Bone marrow showed normocellularity with 41.5% of CD13, 14, 33 positive blasts, and a diagnosis of AMMoL was made. Laboratory investigation revealed hyponatremia and elevated serum ADH level, indicating the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Intensive chemotherapy successfully induced hematological complete remission and his serum sodium level became normal. In February 1992, he developed proteinuria and findings were consistent with nephrotic syndrome (NS). Renal biopsy specimen showed membranous proliferative glomerulonephritis and massive infiltration of macrophages, and his serum interleukin 6 level was elevated. Five months later, he suffered from pancytopenia and elevation of biliary enzymes with increase of hemophagocytic histiocytes in his bone marrow (hemophagocytic syndrome). He transiently responded to low dose chemotherapy but he died due to severe infection. It is interesting that association between macrophages and/or cytokines with these various complications was suggested in AMMoL.

Fatal Outcome↗

PubMed1995

[Aplastic anemia with giant splenomegaly and myelofibrosis successfully treated with antilymphocyte globulin].

Severe aplastic anemia was diagnosed in a 58-year-old female because of pancytopenia with leukocyte count 700/microliters, hemoglobin 3.4 g/dl, platelet count 4.2 x 10(4)/microliters and fatty hypoplastic bone marrow in August 1992. In January 1993, she was admitted with an abdominal skin infection caused by pseudomonas aeruginosa. After treatment of the infection, antilymphocyte globulin was given at a dose of 2,000 mg/day for four consecutive days in July 1993. This resulted in a gradual but steady improvement in her hematological data. In February 1995, her leukocyte count increased to 2,000/microliters, hemoglobin to 15.2 g/dl and platelet count to 11.0 x 10(4)/microliters. Although no splenomegaly or myelofibrosis was found previously, from April 1993, the spleen enlarged and was palpable 10 cm below the costal margin. Her bone marrow biopsy in June 1993 revealed prominent myelofibrosis. Thereafter no changes were found in these features. Splenomegaly and myelofibrosis are characteristic of primary myelofibrosis and although the relationship is uncertain, there is no previous report on aplastic anemia with splenomegaly and myelofibrosis.

Anemia, Aplastic↗

PubMed1995

[A clinical experience of DNA probe method for identifying Mycobacterium avium and Mycobacterium intracellulare].

In Japan the number of patient infected with M. avium complex (MAC) has been increasing in contrast to a decrease of pulmonary tuberculosis. DNA probe method enabled us be able to differentiate an isolated MAC into M. avium and M. intracellulare. From 1991 to 1992, we performed an investigation to apply this new technique of the DNA probe method on 52 patients of atypical mycobacteriosis diagnosed as infected with MAC by the ordinary method at the Higashi Nagoya National Hospital. The group consisted of 27 males and 25 females. M. avium infection was found in 39 patients (M. avium group) and M. intracellulare in 16 patients (M. intracellulare group). No significant gender difference was found between two groups. The M. avium group showed more complications in contrast to the M. intracellulare group. As complications in the M. avium group, pulmonary aspergillus infection, bacterial pneumonia and bronchiectasis were found in 4, 3 and 2 cases, respectively. The rate of drug resistance to antituberculosis drugs was high in the both groups. Chemotherapy with isoniazid (INH) rifampin (RFP) and streptomycin (SM) in five patients, that with INH, RFP and ethambutol (EB) in three were found to be effective after 4 months treatment. Three patients in M. avium group died of respiratory failure, aspergillus infection and renal failure. In contrast the prognosis of patients in the M. intracellulare group seemed to be better as there was no fatal case. We conclude that DNA probe method is useful to differentiate between M. avium and M. intracellulare, and enable us to select more appropriate selection of the chemotherapy and to assess of the prognosis.

Aged↗

PubMed1995

[Bilateral ankle ulcers associated with hydroxyurea therapy for chronic myelogenous leukemia].

Bilateral ankle skin ulcers developed in a 61-year-old man in the chronic phase of chronic myelogenous leukemia receiving hydroxyurea therapy. The circulating immune complex (anti-C3d antibody) was high in this case, but vasculitis was not observed in the pathological findings of biopsied skin materials. This association has been reported in patients who had chronic myelogenous leukemia or other myeloproliferative disorders and were treated with hydroxyurea. It is likely that skin ulcers are caused by hydroxyurea.

Foot Ulcer↗

PubMed1994

Genetic analysis of Escherichia coli O9 rfb: identification and DNA sequence of phosphomannomutase and GDP-mannose pyrophosphorylase genes.

Subcloning, transposon insertion, and deletion analysis revealed that the Escherichia coli O9 rfb region is about 12 kb in size. The region encodes at least seven polypeptides of 89, 74, 55, 50, 44, 41 and 39.5 kDa. Southern hybridization analysis of rfb regions of E. coli O8 and O9, and Klebsiella O3 and O5 serotypes (all of these O polysaccharides are mannose homopolymers and the structures of the repeating unit of E. coli O9 and Klebsiella O3 are identical) showed that a central region specific for E. coli O9 and Klebsiella O3 is flanked by two regions common to all four. Complementation experiments using strains with known defects and specific tests for the enzymic activity showed that the 50 and 55 kDa polypeptides, encoded by the common region, are phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GMP), respectively. Nucleotide sequencing of the region revealed the presence of two genes, rfbK and rfbM, analogous to the corresponding genes of Salmonella typhimurium. In E. coli O9, rfbK and rfbM encode proteins of 460 amino acids (50,809 Da) and 471 amino acids (52,789 Da). The amino acid sequence of GMP was conserved in RfbMs of E. coli O7 and Salmonella groups B, C1 and C2, CpsB of S. typhimurium, AlgA of Pseudomonas aeruginosa, and XanB of Xanthomonas campestris. The phylogenetic trees of PMM and GMP were different in topology and in the evolutionary distances from ancestors.

Amino Acid Sequence↗

PubMed1994

Hypercapnic acidosis increases oxygen cost of contractility in the dog left ventricle.

The effect of acidosis on left ventricular (LV) mechanoenergetics was assessed in seven excised, cross-circulated dog hearts with the use of the frameworks of the contractility index (Emax) and the relationship between myocardial oxygen consumption (VO2) and pressure-volume area (PVA; a measure of the LV total mechanical energy). Acidosis was stably maintained without hypoxia by appropriately mixing CO2 and air in a membrane oxygenator in the coronary arterial perfusion circuit. Acidosis [pH: 6.98 +/- 0.09 (SD), PCO2: 91 +/- 25 mmHg in the coronary arterial blood] decreased Emax by 45 +/- 12% (P < 0.01) and PVA by 47 +/- 12% (P < 0.01) at a fixed LV volume. When the preacidosis Emax level was restored by Ca2+ infusion during acidosis, unloaded VO2 (the VO2 intercept of the VO2-PVA relation) exceeded the control value by 19 +/- 17% (P < 0.05), indicating that acidosis required higher VO2 for nonmechanical activities at a matched Emax. Moreover, the oxygen cost of enhanced contractility (the incremental ratio of unloaded VO2 to Emax) was 1.53 +/- 0.40 times higher (P < 0.01) during acidosis than preacidosis. We conclude that acidosis results in LV contractile dysfunction accompanied by an increased oxygen cost of contractility. This increased energy cost of the excitation-contraction coupling can be accounted for by a decreased Ca2+ sensitivity of the contractile proteins during acidosis.

Acidosis↗

PubMed1994

Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of contractility and the role of the Na(+)-H+ exchange system.

Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloid-perfused hearts after correction of acidosis. In contrast, we have found that, in blood-perfused hearts, contractile function is paradoxically depressed after correction of acidosis with a transient overshoot of contractility during the recovery of pH. To clarify the mechanism of this phenomenon, we measured the LV contractility index (Emax) and the relation between myocardial oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of the LV total mechanical energy) before and after induction and rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised cross-circulated canine hearts. During the rapid correction of acidosis in six control hearts, a severe transient overshoot of Emax (404% of acidosis) occurred. However, after correction of acidosis, Emax and PVA were lower than the preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When the preacidosis Emax level was restored by Ca2+ infusion, the VO2 intercept (PVA-independent VO2) of the linear VO2-PVA relation exceeded the control value by 18% (P < .05) with an unchanged slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased by 83% (P < .01) after correction of acidosis, indicating that postacidosis myocardium requires higher VO2 for nonmechanical activities for a unit increase in Emax. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca2+ overload via accelerated Na(+)-Ca2+ exchange due to the heavily operating Na(+)-H+ exchange system at the time of rapid pH recovery. To examine this hypothesis, dimethylamiloride, a selective Na(+)-H+ exchange inhibitor, was administered just before the correction of acidosis in the other seven hearts. The administration of dimethylamiloride completely prevented both the mechanical and energetic disorders after correction of acidosis. We conclude that rapid recovery of pH paradoxically depresses myocardial contractility and increases the oxygen cost of contractility through an activation of the Na(+)-H+ exchange system.

Acidosis↗