Quantitative relationships between left ventricular ejection and wall thickening and geometry.

The quantitative relationships that exist between left ventricular (LV) wall shortening, wall thickening, and geometry during LV ejection are not well defined. We used a mathematical model to measure these parameters in 40 patients with various LV geometries studied by echocardiography. As opposed to wall shortening, the percent contribution of wall thickening to LV ejection (% delta Vh) was 25 +/- 2% in normal subjects; in all the patients, it varied from 18 to 45% and was inversely correlated (r = 0.94) to the midwall radius-to-wall thickness ratio (R/h) of the ventricle at end diastole. On the other hand, the ratio of the quantity of blood ejected per unit of LV wall volume magnitude of delta V/V omega magnitude of varied from 0.20 to 1.20 (normal subjects 0.83 +/- 0.11) and was directly correlated (r = 0.94) to R/h; using independent data in the literature, we also found a similar relationship (r = 0.80) between the ratio of quantity of blood ejected per unit of LV mass (magnitude of delta V/M omega magnitude of) and R/h. Patients with presumably abnormal myocardial function did not satisfy the relationship between magnitude of delta V/V omega magnitude of or magnitude of delta V/M omega magnitude of and R/h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise.

Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 microg x kg(-1) x min(-1) (SD 6.6) to 42.7 microg x kg(-1) x min(-1) (SD 12.9) vs. women: 23.5 microg x kg(-1) x min(-1) (SD 4.0) to 30.0 microg x kg(-1) x min(-1) (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 microg x kg(-1) x min(-1) (SD 5.1) to 37.0 microg x kg(-1) x min(-1) (SD 11.5) vs. women: 22.6 microg x kg(-1) x min(-1) (SD 6.4) to 30.7 microg x kg(-1) x min(-1) (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.     

Cerebral arteriolar structure and function in pinealectomized rats

We examined cerebral arteriolar structure and autoregulation of cerebral blood flow (CBF) in control (n = 8), sham-operated (n = 8), pinealectomized (n = 10), and pinealectomized plus melatonin-treated (0.51 +/- 0.01 mg x kg(-1) x day(-1) in drinking water, n = 9) young Wistar rats. The lower limit of CBF autoregulation (LLCBF) was determined by measurement of CBF (in arbitrary units, laser Doppler) during stepwise hypotensive hemorrhage; the arteriolar internal diameter (ID; in microm, cranial window) was also measured. Measurements of ID were repeated during a second stepwise hypotension after smooth muscle cell deactivation (67 mmol/l EDTA). The cross-sectional area (CSA) was measured by histometry. CSA and EDTA-induced vasodilatation decreased after pinealectomy (517 +/- 21 vs. 819 +/- 40 microm(2) in sham and 829 +/- 55 microm(2) in control, P < 0.05, and 81 +/- 4 vs. 102 +/- 5 microm in sham and 104 +/- 4 microm in control, P < 0.05, respectively) and were restored by melatonin (924 +/- 39 microm(2) and 102 +/- 5 microm, respectively). These results suggest that melatonin deprival makes the arteriolar wall thinner and stiffer. However, these changes had little effect on LLCBF. In conclusion, pinealectomy of young rats induces atrophy and decreases distensibility of the cerebral arteriolar wall; these effects are prevented by melatonin. They do not modify LLCBF.     

Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats

Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 microm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.     

Functional medial thickening and folding of the internal elastic lamina in coronary spasm

Although there are a number of studies on vasospastic angina, the structural changes at the cellular level that occur in the coronary arterial wall during spasm are not well known. Coronary spasm was induced by brushing the coronary adventitia in nine anesthetized beagles, and structural changes in the spastic coronary segments were examined by light and electron microscopy, making comparisons with the adjacent nonspastic segments. The % diameter stenosis of the spastic segments as measured angiographically was 79.4±12% (mean±SD). Light microscopic changes in the spastic and nonspastic segments were as follows: medial thickness 1,512 vs. 392 μm (P<0.0001) and % diameter and % area stenoses of spastic segment 81.0% and 96.5%, respectively, indicating that spasm was induced by medial thickening. Circular smooth muscle cells (SMCs) in the media were arranged in parallel with the internal (IEL) and external (EEL) elastic lamina in nonspastic segments but radially rearranged in spastic segments. SMCs were classified by their patterns of connection to IEL into six types by electron microscopy. Of these, three contracted and pulled the IEL toward the EEL, causing folding of the IEL and waving of EEL resulting in thickening of the media and narrowing of the lumen. We conclude that coronary spasm was elicited by radial rearrangement of the medial SMCs due to their own contraction and resultant medial thickening and folding of IEL, creating a piston effect to narrow the lumen, i.e., spasm.     

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats.

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LV(M)) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC ( approximately 45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/dt) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LV(M) and +dP/dt-to-LV(M) ratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/dt-to-LV(M) ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.     

Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats

This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus (E(m)) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28-0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004-0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50-0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.     

Change n the ploidy classes of left ventricular myocytes in rats after ligation of the left coronary artery

Heterogeneous response of cardiomyocytes in left atria of rats to ligation of the left coronary artery was observed. Ploidy may greatly increase reaching 32 c per cell. More than 90% of myocytes are normally mononuclear diploid cells, while after the ligation the number of such cells diminishes to 10%. The majority of cells become polyploid: above 50% of cells are 2 X 2 c ploid, about 30% of cells are 4 X 2 c ploid and a great number of cells are highly ploid.     

Mechanosensitive cardiac C-fiber response to changes in left ventricular filling, coronary perfusion pressure, hemorrhage, and volume expansion in rats

Left ventricular (LV) end-diastolic pressure (LVEDP) increase due to volume expansion (VExp) enhances mechanosensitive vagal cardiac afferent C-fiber activity (CNFA), thus decreasing renal sympathetic nerve activity (RSNA). Hypotensive hemorrhage (hHem) attenuates RSNA despite decreased LVEDP. We hypothesized that CNFA increases with any change in LVEDP. Coronary perfusion pressure (CPP), supposedly affected in both conditions, might also be a stimulus of CNFA. VExp and hHem were performed in anesthetized male Sprague-Dawley rats while blood pressure, heart rate, and RSNA were measured. Cervical vagotomy abolished RSNA response in both reflex responses. Single-unit CNFA was recorded while LVEDP was changed. Rapid changes (+/- 4, +/-6, +/-8 mmHg) were obtained by graded occlusion of the caval vein and descending aorta. Prolonged changes were obtained by VExp and hHem. Furthermore, CNFA was recorded in a modified Langendorff heart while CPP was changed (70, 100, 40 mmHg). Rapid LVEDP changes increased CNFA [caval vein occlusion: +16 +/- 3 Hz (approximately +602%); aortic occlusion: +15 +/- 3 Hz (approximately +553%); 70 units; P < 0.05]. VExp and hHem (n = 6) increased CNFA [VExp: +10 +/- 4 Hz (approximately +1,033%); hHem: +10 +/- 2 Hz (approximately +1,225%); P < 0.05]. An increase in CPP increased CNFA [+2 +/- 1 Hz (approximately +225%); P < 0.05], whereas a decrease in CPP decreased CNFA [-0.8 +/- 0.4 Hz (approximately -50%); P < 0.05]. All C fibers recorded originated from the LV. CNFA increased with any LVEDP change but changed equidirectionally with CPP. Thus neither LVEDP nor CPP fully accounts directly for afferent C-fiber and reflex sympathetic responses. The intrinsic afferent stimuli and receptive fields accounting for reflex sympathoinhibition still remain cryptic.     

Pregnancy failure in hypophysectomized rats following LH-RH administration.

Daily LH-RH administration induced a dose related increase in fetal resorption in rats following hypophysectomy on Day 11 or Day 12 of pregnancy. Ovarian and adrenal weights, as well as serum progesterone levels, were significantly decreased by Day 18. Serum progesterone was also significantly lower than control in those animals that remained pregnant after receiving LH-RH post-hypophysectomy. These observations suggest that LH-RH exerts an anti-pregnancy effect via a placental:ovarian axis in this species.     

Hydrogen sulfide improves left ventricular function in smoking rats via regulation of apoptosis and autophagy

The present study was designed to investigate the protective effects of hydrogen sulfide (H₂S) against cigarette smoking-induced left ventricular dysfunction in rats. Left ventricular structure and function were assessed using two-dimensional echocardiography. Cardiomyocyte apoptosis was determined by Annexin V/PI and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Cardiac autophagy was evaluated by detection of autophagy-related protein expression and observation of autophagosomes. Our results indicated that administration of NaHS (a donor of H₂S) could protect against smoking-induced left ventricular systolic dysfunction. H₂S was found to exert anti-apoptotic effects in the myocardium of smoking rats by inhibiting JNK and P38 mitogen-activated protein kinases pathways and activating PI3K/Akt signaling. Moreover, H₂S could also reduce smoking-induced autophagic cell death via regulation of AMPK/mTOR signaling pathway. In conclusion, our study demonstrates that H₂S can improve left ventricular systolic function in smoking rats via regulation of apoptosis and autophagy.     

Predictive value of left ventricular function on prognosis in patients undergoing coronary artery bypass surgery

In order to assess the predictive value of left ventricular (LV) function on prognosis during 16 years of follow-up we retrospectively/prospectively evaluated 320 patients (mean age 55.9 +/- 9.2 years; 44 women, 276 men) undergoing coronary artery bypass surgery. Patients were divided according to the assessed echocardiographically pre- and postoperative LV ejection fraction (LVEF) into two groups: patients with LV dysfunction (EF < 55%) and patients with preserved LV function (EF >or= 55%). In order to assess the prognostic variables, patients were further subdivided into a group with severely depressed LV function (EF 相似文献   

Adrenal glucocorticoid function in rats with various ethanol-induced sleeping time following ethanol administration

The effect of single and chronic ethanol (Eth) administration (25 % solution, 3.5 g/kg) on functional activity of the hypophyseal-adrenal system in rats with different sensitivity to the hypnotic action of ethanol (short-sleep - SS; non-sleep--NS, long-sleep--LS, intermediate group--IG), was studied. It has been shown that, after a single Eth administration, the concentration of corticosterone (K) in LS rat plasma was 1.5-fold higher than that in the NS animals although it did not differ from the K level in SS and Ig those. After repeated ethanol load, the corticosterone contents in the NS rat blood plasma was 3.5-fold and 4.9-fold lower compared to the control and LS groups, respectively. The data obtained indicate that the SS and LS animals had initially different basal blood plasma glucocorticoid level. The SS animals showed a decreased blood plasma K, whereas the LS ones--an increased one. The features of the glucocorticoid status are suggested to be a factor determining the sensitivity of rats to the ethanol hypnotic effect.     

Electromechanical stimulation ameliorates inactivity-induced adaptations in the medial gastrocnemius of adult rats.

The efficacy of high-load, short-duration isometric contractions, delivered as one vs. two sessions per day, on blunting inactivity-induced adaptations in the medial gastrocnemius (MG) were compared. Adult rats were assigned to a control (Con) or spinal cord-isolated (SI) group where one limb was stimulated (SI-Stim) while the other served as a SI control (SI-C). One bout of stimulation (BION microstimulator) consisted of a 100-Hz, 1-s stimulus, delivered every 30 s for 5 min with a 5-min rest period. This bout was repeated six times consecutively (SI-Stim1) or with a 9-h rest interval after the third bout (SI-Stim2) for 30 consecutive days. MG weights (relative to body weight) were 63, 72, and 79% of Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Mean fiber size was 56% smaller in SI-C than in Con, and it was 19 and 31% larger in SI-Stim1 and SI-Stim2, respectively, compared with SI-C. Maximum tetanic tension was 42, 60, and 73% of Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Specific tension was 77% of Con in SI-C, and at Con levels in both SI-Stim groups. SI increased the percent IIb myosin heavy chain composition (from 49 to 77%) and IIb+ fibers (from 63 to 79%): these adaptations were prevented by both Stim paradigms. These results demonstrate that 1) brief periods of high-load isometric contractions are effective in reducing inactivity-induced atrophy, functional deficits, and phenotypic adaptations in a fast hindlimb extensor, and 2) the same amount of stimulation distributed in two compared with one session per day is more effective in ameliorating inactivity-related adaptations.     

Heterogeneous Kv1 function and expression in coronary myocytes from right and left ventricles in rats

Coronary blood flow control is not uniform along the vascular tree and particularly between the right coronary artery and the left anterior descending artery. Resting membrane potential that contributes largely to the vascular tone is mainly regulated by K(+) channels in coronary myocytes. In the present study, we hypothesized that right coronary artery (RCA) and left coronary artery (LCA) exhibited a cell-specific function of K(+) channels. The net outward current was markedly greater in RCA compared with LCA cells, and this difference was due to a larger 4-aminopyridine (4-AP)-sensitive voltage-gated potssium (Kv) current in RCA cells, whereas the iberiotoxin (IbTx)-sensitive, large conductance Ca(2+)-dependent potassium (BK(Ca)) current was smaller in RCA cells. To go further in the molecular identity of this Kv current, we used 50 nM correolide, which specifically blocked Kv1 family alpha-subunits. Outward currents generated by ramp depolarization protocols were highly sensitive to correolide in both RCA and LCA cells, suggesting that Kv1 contributed for a large part to the net outward current. 4-AP-induced contractions in isolated RCA, and LCA were greater than IbTx-induced contraction. Furthermore, the 4-AP-induced contraction in RCA was significantly greater than that in LCA, which is in agreement with the electrophysiological data. Finally, the Kv1.2 alpha-subunit but not the Kv1.5 was detected in both RCA and LCA using primary specific antibody in Western blotting and immunofluorescence assay, and expression of Kv1.2 alpha-subunit was markedly higher in RCA compared with LCA. In summary, we reported for the first time a heterogeneous function and expression of Kv1 alpha-subunits in rat coronary myocytes isolated from RCA or LCA.