Relation between outer and luminal diameter in cannulated arteries. (73/3898)

Resistance in blood vessels is directly related to the inner (luminal) diameter (ID). However, ID can be difficult to measure during physiological experiments because of poor transillumination of thick-walled or tightly constricted vessels. We investigated whether the wall cross-sectional area (WCSA) in cannulated arteries is nearly constant, allowing IDs to be calculated from outer diameters (OD) using a single determination of WCSA. With the use of image analysis, OD and ID were directly measured using either transillumination or a fluorescent marker in the lumen. IDs from a variety of vessel types were calculated from WCSA at several reference pressures. Calculated IDs at all of the reference WCSA were within 5% (mean <1%) of the corresponding measured IDs in all vessel types studied, including vessels from heterozygote elastin knockout animals. This was true over a wide range of transmural pressures, during treatment with agonists, and before and after treatment with KCN. In conclusion, WCSA remains virtually constant in cannulated vessels, allowing accurate determination of ID from OD measurement under a variety of experimental conditions.  (+info)

Weibull distribution function for cardiac contraction: integrative analysis. (74/3898)

The Weibull distribution is widely used to analyze the cumulative loss of performance, i.e., breakdown, of a complex system in systems engineering. We found for the first time that the difference curve of two Weibull distribution functions almost identically fitted the isovolumically contracting left ventricular (LV) pressure-time curve [P(t)] in all 345 beats (3 beats at each of 5 volumes in 23 canine hearts; r = 0.999953 +/- 0.000027; mean +/- SD). The first derivative of the difference curve also closely fitted the first derivative of the P(t) curve. These results suggest the possibility that the LV isovolumic P(t) curve may be characterized by two counteracting cumulative breakdown systems. Of these, the first breakdown system causes a gradual pressure rise and the second breakdown system causes a gradual pressure fall. This Weibull-function model of the heart seems to give a new systems engineering or integrative physiological view of the logic underlying LV isovolumic pressure generation.  (+info)

Sequential gating in the human heart K(+) channel Kv1.5 incorporates Q(1) and Q(2) charge components. (75/3898)

On-gating current from the Kv1.5 cardiac delayed rectifier K(+) channel expressed in HEK-293 cells was separated into two distinct charge systems, Q(1) and Q(2), obtained from double Boltzmann fits to the charge-voltage relationship. Q(1) and Q(2) had characteristic voltage dependence and sensitivity with half-activation potentials of -29.6 +/- 1.6 and -2.19 +/- 2.09 mV and effective valences of 1. 87 +/- 0.15 and 5.53 +/- 0.27 e(-), respectively. The contribution to total gating charge was 0.20 +/- 0.04 for Q(1) and 0.80 +/- 0.04 (n = 5) for Q(2). At intermediate depolarizations, heteromorphic gating current waveforms resulted from relatively equal contributions from Q(1) and Q(2), but with widely different kinetics. Prepulses to -20 mV moved only Q(1), simplified on-gating currents, and allowed rapid Q(2) movement. Voltage-dependent on-gating current recovery in the presence of 4-aminopyridine (1 mM) suggested a sequentially coupled movement of the two charge systems during channel activation. This allowed the construction of a linear five-state model of Q(1) and Q(2) gating charge movement, which predicted experimental on-gating currents over a wide potential range. Such models are useful in determining state-dependent mechanisms of open and closed channel block of cardiac K(+) channels.  (+info)

Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia. (76/3898)

Ventricular fibrillation (VF), the major cause of sudden cardiac death, is typically preceded by ventricular tachycardia (VT), but the mechanisms underlying the transition from VT to VF are poorly understood. Intracellular Ca(2+) overload occurs during rapid heart rates typical of VT and is also known to promote arrhythmias. We therefore studied the role of intracellular Ca(2+) dynamics in the transition from VT to VF, using a combined experimental and mathematical modeling approach. Our results show that 1) rapid pacing of rabbit ventricular myocytes at 35 degrees C led to increased intracellular Ca(2+) levels and complex patterns of action potential (AP) configuration and the intracellular Ca(2+) transients; 2) the complex patterns of the Ca(2+) transient arose directly from the dynamics of intracellular Ca(2+) cycling, and were not merely passive responses to beat-to-beat alterations in AP; 3) the complex Ca(2+) dynamics were simulated in a modified version of the Luo-Rudy (LR) ventricular action potential with improved intracellular Ca(2+) dynamics, and showed good agreement with the experimental findings in isolated myocytes; and 4) when incorporated into simulated two-dimensional cardiac tissue, this action potential model produced a form of spiral wave breakup from VT to a VF-like state in which intracellular Ca(2+) dynamics played a key role through its influence on Ca(2+)-sensitive membrane currents such as I(Ca), I(NaCa), and I(ns(Ca)). To the extent that spiral wave breakup is useful as a model for the transition from VT to VF, these findings suggest that intracellular Ca(2+) dynamics may play an important role in the destabilization of VT and its degeneration into VF.  (+info)

Energetics of Na(+)-Ca(2+) exchange in resting cardiac muscle. (77/3898)

The energetic effect of extracellular Na(+) removal and readmission (in a nominally Ca(2+)-free perfusate) in Langendorff-perfused ventricles of transgenic mice (TM), which overexpress the sarcolemmal Na(+)-Ca(2+) exchanger; normal mice (NM); young (7-12 days old) rats (YR); and older (13-20 days old) rats (OR) was studied. In all heart muscles, extracellular Na(+) removal induced an increase in heat production (H(1)). Na(+) readmission further increased heat production to a peak value (H(2)) followed by a decrease toward initial values. These effects were more marked in the YR and TM as compared with the OR and NM groups, respectively. Caffeine (1 mM), ryanodine (0.2 microM), and verapamil (1 microM) decreased H(1) and H(2) in both rat groups. EGTA (1 mM) decreased H(1) and H(2) in the YR but not in the OR group. Thapsigargin (1 microM) decreased H(1) and H(2) in all four hearts preparations. A possible interpretation is that Na(+)-Ca(2+) exchange acts as an energy-saving mechanism to prevent Ca(2+) accumulation at the junctional sarcoplasmic reticulum zone (JSR) and thus prevents further release of Ca(2+). Extracellular Na(+) removal lead to Ca(2+) accumulation in the JSR inducing further SR-Ca(2+) release and increased energy release. Na(+) readmission removes the accumulated Ca(2+) at the JSR (cleft) zone by exchanging Ca(2+) with Na(+) producing a transitory increase in energy release due to Na(+)-K pump activation.  (+info)

Efficacy of a filter device in the prevention of embolic events during carotid angioplasty and stenting: An ex vivo analysis. (78/3898)

OBJECTIVE: Although percutaneous angioplasty and stenting (PTAS) of carotid bifurcation lesions is feasible and appropriate for surgically inaccessible lesions, its general role and comparative value remain unclarified. Moreover, the acceptance of carotid PTAS has been limited by its potential for producing embolic debris. This study used an ex vivo model to evaluate the efficacy of a novel filter device to entrap emboli during PTAS of human carotid plaques. METHODS: Eight carotid bifurcation plaques were obtained from patients who underwent carotid endarterectomy for high-grade atherosclerotic stenosis (>90%). The mean age of the patients was 63 years, and six patients were symptomatic. Each plaque was encased with polytetrafluoroethylene material to simulate adventitia and was connected to a perfusion circuit, which provided continuous flow through the plaque. The filter device consisted of an expandable polymeric membrane with multiple micro pores that was attached to the distal end of a 0.014-in wire with a shapeable tip. This filter was encased in a delivery catheter. With fluoroscopic guidance, the filter wire was passed through the stenosis and the delivery catheter was then retracted to open the filter to capture particles released into the distal internal carotid artery. PTAS with a self-expandable stent then was carried out over the filter wire. The particles released during the initial filter passage, those captured in the filter, and those that flowed through or around the filter (missed) were collected and analyzed with light microscopy. RESULTS: Filter deployment, PTAS, and filter retrieval were achieved successfully with each lesion. Because the filter has a low crossing profile, it passed through the stenoses smoothly and only produced occasional small particles. PTAS improved the angiographic stenosis from 96.2% +/- 3.7% to 1.3% +/- 1.6%. The mean number and the maximum size of the particles that were released during initial filter passage, missed, and captured by the filter device were 3.1 and 500 microm, 2.8 and 360 microm, 20.1 and 1100 microm, respectively. Most of the particles and those of large size were released during PTAS. The filter captured 88% of these particles. CONCLUSION: These study results show that this filter device, at least in this model, did not add complexity to the interventional procedure itself. Furthermore, the filter may markedly decrease embolic events during carotid PTAS and expand the indications for this procedure.  (+info)

Hemodynamic patterns and spectral analysis of heart rate variability during dialysis hypotension. (79/3898)

Intradialytic hypotension, a major source of morbidity during hemodialysis and ultrafiltration, is often accompanied by paradoxical bradycardia. Relatively little is known about the sequential changes in autonomic nervous system activity up to and during the hypotensive episode. Continuous, beat-to-beat measurements of BP and heart rate were made during hemodialysis in patients prone (n = 8) and not prone (n = 11) to develop intradialytic hypotension. Off-line spectral analysis of heart rate variability (HRV) was performed to assess changes in autonomic nervous system activity during dialysis sessions both with and without hypotension. The low frequency (LF) component of HRV is thought to correlate with sympathetic nervous system activity, the high frequency (HF) component with that of the parasympathetic nervous system. In the sessions not complicated by symptomatic hypotension (n = 26), mean arterial BP (MAP) hardly fell, whereas heart rate increased from 77 +/- 2 to 89 +/- 5 bpm (P < 0.05). The LF component of HRV increased from 45.2 +/- 5.0 normalized units (nu) to 59.9 +/- 4.9 nu (P < 0.05), whereas the HF component fell from 54.8 +/- 5.0 to 40.2 +/- 4.4 nu (P < 0.05). These changes agree with compensatory baroreflex-mediated activation of the sympathetic nervous system (and suppressed parasympathetic activity) during ultrafiltration-induced intravascular volume depletion. In the sessions complicated by severe symptomatic hypotension (n = 22), the changes in heart rate and the results of spectral analysis of HRV were similar to those reported above up to the moment of sudden symptomatic (nausea, vomiting, dizziness, cramps) hypotension, whereas MAP had already fallen gradually from 94 +/- 3 to 85 +/- 3 mmHg (P < 0.05). The sudden further reduction in MAP (to 55 +/- 2 mmHg, P < 0.02) was invariably accompanied by bradycardia (heart rate directly before hypotension 90 +/- 2 bpm, during hypotension 69 +/- 3 bpm, P < 0.002). The LF component of HRV fell from 62.8 +/- 4.6 nu directly before to 40.0 +/- 3.7 nu (P < 0.05) during hypotension, whereas the HF component increased from 37.9 +/- 4.7 to 60.3 +/- 3.7 nu (P < 0.05). These findings agree with activation of the cardiodepressor reflex, involving decreased sympathetic and increased parasympathetic nervous system activity, respectively. These findings indicate that activation of the sympatho-inhibitory cardiodepressor reflex (Bezold-Jarisch reflex), which is a physiologic response to a critical reduction in intravascular volume and cardiac filling, is the cause of sudden intradialytic hypotension.  (+info)

Different patterns of angiogenesis in sarcomas and carcinomas. (80/3898)

Solid tumors depend on angiogenesis for growth and metastasis. It has been shown that blood vessel density, as determined by counting the number of capillaries in clustered bursts, is a significant prognostic factor in carcinomas. It is unclear, however, whether vessel density is a prognostic factor in sarcomas. In this study, we examined angiogenesis in sarcomas of various grades and compared their vascular patterns to those of carcinomas. Microvessels were identified by von Willebrand factor staining. The matrix of multiple sarcoma and breast carcinoma specimens were extracted and subjected to Western analysis of various angiogenic factors and inhibitors. Metalloproteinase inhibitor presence was also determined by in situ hybridization. In breast carcinomas, capillaries were clustered in bursts within the stroma of the tumor, whereas the sarcoma capillaries were homogeneously distributed in the tumor stroma. Random blood vessel density per high power field in sarcomas did not correlate with patient prognosis. The matrix of sarcomas and carcinomas contained both angiogenic stimulators and inhibitors. Tissue inhibitor of metalloproteinase-1 was found predominantly in fibroblasts and myofibroblasts in the matrix of carcinoma specimens. The difference in the pattern of angiogenesis in sarcomas and carcinomas may be attributable to the presence of fibroblasts and myofibroblasts in carcinomas, resulting in the compartmentalization of bursts of angiogenic factors. The homogeneous appearance of vessel density in sarcomas observed in the present study would be the consequence of the influence of a single compartment.  (+info)