Biomedical subjects

S Kohin

Publications and source records attributed to S Kohin.

9 recordsLinked to original sources

PubMed2003

Trimetazidine reduces basal cytosolic Ca2+ concentration during hypoxia in single Xenopus skeletal myocytes.

We tested the hypotheses that: (1) Ca(2+) handling and force production would be irreversibly altered in skeletal muscle during steady-state contractions when subjected to severe, prolonged hypoxia and subsequent reoxygenation; and (2) application of the cardio-protective drug trimetazidine would attenuate these alterations. Single, living skeletal muscle fibres from Xenopus laevis were injected with the Ca(2+) indicator fura 2, and incubated for 1 h prior to stimulation in 100 micro M TMZ-Ringer solution (TMZ; n = 6) or standard Ringer solution (CON; n = 6). Force and relative free cytosolic Ca(2+) concentration ([Ca(2+)](c)) were measured during continuous tetanic contractions produced every 5 s as fibres were sequentially perfused in the following manner: 3 min high extracellular P(O(2)) (159 mmHg), 15 min hypoxic perfusion (3-5 mmHg) then 3 min high P(O(2)). Hypoxia caused a decrease in force and peak [Ca(2+)](c) in both the TMZ and CON fibres, with no significant (P < 0.05) difference between groups. However, basal [Ca(2+)](c) was significantly lower during hypoxia in the TMZ group vs. the CON group. While reoxygenation generated only modest recovery of relative force and peak [Ca(2+)](c) in both groups, basal [Ca(2+)](c) remained significantly less in the TMZ group. These results demonstrated that in contracting, single skeletal muscle fibres, TMZ prevented increases in basal [Ca(2+)](c) generated during a severe hypoxic insult and subsequent reoxygenation, yet failed to protect the cell from the deleterious effects of prolonged hypoxia followed by reoxygenation.

Animals↗

PubMed2001

A killer appetite: metabolic consequences of carnivory in marine mammals.

Among terrestrial mammals, the morphology of the gastrointestinal tract reflects the metabolic demands of the animal and individual requirements for processing, distributing, and absorbing nutrients. To determine if gastrointestinal tract morphology is similarly correlated with metabolic requirements in marine mammals, we examined the relationship between basal metabolic rate (BMR) and small intestinal length in pinnipeds and cetaceans. Oxygen consumption was measured for resting bottlenose dolphins and Weddell seals, and the results combined with data for four additional species of carnivorous marine mammal. Data for small intestinal length were obtained from previously published reports. Similar analyses were conducted for five species of carnivorous terrestrial mammal, for which BMR and intestinal length were known. The results indicate that the BMRs of Weddell seals and dolphins resting on the water surface are 1.6 and 2.3 times the predicted levels for similarly sized domestic terrestrial mammals, respectively. Small intestinal lengths for carnivorous marine mammals depend on body size and are comparatively longer than those of terrestrial carnivores. The relationship between basal metabolic rate (kcal day(-1)) and small intestinal length (m) for both marine and terrestrial carnivores was, BMR=142.5 intestinal length(1.20) (r(2)=0.83). We suggest that elevated metabolic rates among marine mammal carnivores are associated with comparatively large alimentary tracts that are presumably required for supporting the energetic demands of an aquatic lifestyle and for feeding on vertebrate and invertebrate prey.

Animals↗

PubMed2001

Preconditioning improves function and recovery of single muscle fibers during severe hypoxia and reoxygenation.

Reperfusion following prolonged ischemia induces cellular damage in whole skeletal muscle models. Ischemic preconditioning attenuates the deleterious effects. We tested whether individual skeletal muscle fibers would be similarly affected by severe hypoxia and reoxygenation (H/R) in the absence of extracellular factors and whether cellular damage could be alleviated by hypoxic preconditioning. Force and free cytosolic Ca2+ ([Ca2+]c) were monitored in Xenopus single muscle fibers (n = 24) contracting tetanically at 0.2 Hz during 5 min of severe hypoxia and 5 min of reoxygenation. Twelve cells were preconditioned by a shorter bout of H/R 1 h before the experimental trial. In preconditioned cells, force relative to initial maximal values (P/P(o)) and relative peak [Ca2+]c fell (P < 0.05) during 5 min of hypoxia and recovered during reoxygenation. In contrast, P/P(o) and relative peak [Ca2+]c fell more during hypoxia (P < 0.05) and recovered less during reoxygenation (P < 0.05) in control cells. The ratio of force to [Ca2+]c was significantly higher in the preconditioned cells during severe hypoxia, suggesting that changes in [Ca2+]c were not solely responsible for the loss in force. We conclude that 1) isolated skeletal muscle fibers contracting in the absence of extracellular factors are susceptible to H/R injury associated with changes in Ca2+ handling; and 2) hypoxic preconditioning improves contractility, Ca2+ handling, and cell recovery during subsequent hypoxic insult.

Animals↗

PubMed1999

Effects of hypoxia and hypercapnia on aerobic metabolic processes in northern elephant seals.

An hypoxia-induced metabolic down-regulation has been implicated as an important protective mechanism against tissue deoxygenation in mammals. Whether the same response to hypoxia occurs in northern elephant seals was studied. The effects of hypercapnia were also examined to determine whether the reduced ventilatory response of seals to CO2 is associated with an analogous protective metabolic down-regulation. Thirty three seals (7-300-days-old) were studied using open-flow respirometry with simultaneous monitoring of apnea frequencies and heart rates. Hypoxia (11% O2) and hypercapnia (7% CO2) caused increases in metabolism of up to 38% with corresponding decreases in the percent time spent apneic (%AP) and increases in heart rate. The metabolic, breathing and heart rate responses to altered inspired gases were independent of age. Metabolism was strongly negatively correlated with %AP suggesting that elevated metabolism during hypoxia and hypercapnia exposure is attributable to decreases in %AP. In young elephant seals metabolic down-regulation is not an automatic protective response to experimentally-imposed hypoxia or hypercapnia.

Aerobiosis↗

PubMed1999

Hunting behavior of a marine mammal beneath the antarctic fast Ice

The hunting behavior of a marine mammal was studied beneath the Antarctic fast ice with an animal-borne video system and data recorder. Weddell seals stalked large Antarctic cod and the smaller subice fish Pagothenia borchgrevinki, often with the under-ice surface for backlighting, which implies that vision is important for hunting. They approached to within centimeters of cod without startling the fish. Seals flushed P. borchgrevinki by blowing air into subice crevices or pursued them into the platelet ice. These observations highlight the broad range of insights that are possible with simultaneous recordings of video, audio, three-dimensional dive paths, and locomotor effort.

Journal Article↗

PubMed1999

Rapid force recovery in contracting skeletal muscle after brief ischemia is dependent on O(2) availability.

We tested the hypothesis that contracting skeletal muscle can rapidly restore force development during reperfusion after brief total ischemia and that this rapid recovery depends on O(2) availability and not an alternate factor related to blood flow. Isolated canine gastrocnemius muscle (n = 5) was stimulated to contract tetanically (isometric contraction elicited by 8 V, 0.2-ms duration, 200-ms trains, at 50-Hz stimulation) every 2 s until steady-state conditions of muscle blood flow (controlled by pump perfusion) and developed force were attained (3 min). While maintaining the same stimulation pattern, muscle blood flow was then reduced to zero (complete ischemia) for 2 min. Normal blood flow was then restored to the contracting muscle; however, two distinct conditions of oxygenation (at the same blood flow) were sequentially imposed: deoxygenated blood (30 s), blood with normal arterial O(2) content (30 s), a return to deoxygenated blood (30 s), and finally a return to normal arterial O(2) content (90 s). During the ischemic period, force development fell to 39 +/- 6 (SE)% of normal (from 460 +/- 40 to 170 +/- 20 N/100 g). When muscle blood flow was restored to normal by perfusion with deoxygenated blood, developed force continued to decline to 140 +/- 20 N/100 g. Muscle force rapidly recovered to 310 +/- 30 N/100 g (P < 0.05) during the 30 s in which the contracting muscle was perfused with oxygenated blood and then fell again to 180 +/- 30 N/100 g when perfused with blood with low PO(2). These findings demonstrate that contracting skeletal muscle has the capacity for rapid recovery of force development during reperfusion after a short period of complete ischemia and that this recovery depends on O(2) availability and not an alternate factor related to blood flow restoration.

Animals↗

PubMed1995

Effects of hypertrophy on left atrial and ventricular compliance and plasma ANF levels in conscious dogs.

Alterations in left atrial (LA) and left ventricular (LV) compliance and arterial and coronary sinus atrial natriuretic factor (ANF) concentrations at baseline and in response to both volume depletion and expansion were investigated in 15 conscious dogs with aortic banding-induced LV hypertrophy (LVH) (LV/body wt increased by 64%), which also induced LAH (LA/body wt increased by 61%). With volume expansion coronary sinus ANF increased more (P < 0.05) in dogs with LVH (+427 +/- 88 pg/ml) compared with control dogs (+146 +/- 45 pg/ml). Arterial ANF levels also rose more with volume expansion in LVH. In dogs with LVH, the LV end-diastolic pressure-diameter relationship was shifted to the left with a steeper slope with volume expansion, such that at any given diastolic dimension, diastolic pressure was higher. In contrast, the pressure-dimension relationship for the LA appendage was shifted in the opposite direction during both atrial systolic and diastolic phases, with a more shallow slope in hypertrophy compared with control dogs, resulting in an augmented pressure-dimension product during volume loading in LAH. In conclusion, in dogs with LVH and LAH, enhanced ANF was revealed in the coronary sinus and systemic circulation during volume expansion, which could be due, in part, to a more compliant, but hypertrophied, LA, which responded to equivalent volume loading with an augmented pressure-dimension product.

Animals↗

PubMed1990

Exercise-induced subendocardial dysfunction in dogs with left ventricular hypertrophy.

The effects of treadmill exercise on regional myocardial blood flow and function were examined in 10 adult, conscious dogs with left ventricular hypertrophy (LVH) induced by aortic banding in puppies, which resulted in a left ventricular (LV) weight/body weight ratio of 8.5 +/- 0.3. Data were compared with results from eight control dogs with an LV weight/body weight ratio of 4.9 +/- 0.2. At rest, LV systolic and end-diastolic pressures were significantly greater (p less than 0.01), and mean arterial pressure was significantly less (p less than 0.05) in LVH dogs. Mean myocardial blood flow (control dogs, 0.98 +/- 0.11 ml/min/g; LVH dogs, 1.16 +/- 0.06 ml/min/g) and the transmural blood flow distribution at baseline, as assessed by endocardial/epicardial blood flow ratio (control, 1.35 +/- 0.12; LVH, 1.21 +/- 0.09), were similar in the two groups. During exercise to a target heart rate (240 beats/min), LVH dogs demonstrated greater (p less than 0.01) increases in LV systolic and end-diastolic pressures. In control dogs, as expected, exercise augmented velocity of circumferential fiber shortening (16 +/- 9%) and shortening fraction (15 +/- 5%), but in LVH dogs, exercise reduced the velocity of circumferential fiber shortening (-14 +/- 6%) and shortening fraction (-17 +/- 5%). Exercise also increased full wall thickening (35 +/- 5%), subendocardial wall thickening (66 +/- 10%), and subepicardial wall thickening (44 +/- 9%) in control dogs. In LVH dogs, exercise increased subepicardial wall thickening (31 +/- 9%) and reduced subendocardial wall thickening (-40 +/- 7%); full wall thickening did not change (-11 +/- 9%). This was associated with a fall in endocardial/epicardial flow ratio to 0.72 +/- 0.05 (p less than 0.01) in LVH dogs. The subendocardial dysfunction persisted late into recovery, at a time when the transmural blood flow distribution had returned to baseline; this occurrence suggested myocardial stunning. Thus, in dogs with LVH, selective subendocardial hypoperfusion and profound selective depression in subendocardial wall thickening are observed during exercise. The subendocardial dysfunction persisted into recovery despite resolution of the perfusion abnormality.

Animals↗

PubMed1989

Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure.

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.

Animals↗