Pacing-induced Tachycardia Research Articles

Question: Never skip a beat: pacing-induced polymorphic ventricular tachycardia following inferior myocardial infarction.

Question: Never skip a beat: pacing-induced polymorphic ventricular tachycardia following inferior myocardial infarction.

Lightning-induced pacing system malfunction: a case report.

BackgroundAtmospheric electrical discharge is an extremely powerful natural phenomenon which can have dangerous and lethal effects on the human body. However, there is no evidence to indicate whether and, if so, to what extent the electric current travelling through the body can affect proper pacemaker function.Case summaryAn 80-year-old patient admitted to emergency department after being struck by a lightning bolt while riding a bike. The patient had a DDD pacemaker implanted 4 years prior to the incident. The ECG on admission depicted pacemaker spikes and native sinus rhythm at 50–60 b.p.m. On the 3rd day after admission the patient developed recurrent pacing-induced tachycardia. Pacemaker interrogation showed high pacing thresholds (failure to pace in the atrial channel). When the patient’s condition stabilized she was transferred to the tertiary hospital for transcutaneous lead extraction. The extracted pacing system was sent to Biotronik for thorough evaluation.DiscussionInjuries due to a lightning strike are considered a rare occurrence but being struck by lightning with a pacemaker or an ICD is even less common. In the present case, the cause of cardiac arrhythmia was most probably electrical burn at the endocardial-electrode interface and a sudden elevation of the pacing threshold leading to transient pacing failure in both PM channels. To the best of our knowledge, in this case presentation we first described permanent lightning-induced pacemaker dysfunction.

Oscillatory behavior of P wave duration and PR interval in experimental congestive heart failure: a preliminary study

Objective: The relationship between the autonomic nervous system (ANS) modulation of the sinus node and heart rate variability has been extensively investigated. The current study sought to evaluate, in an animal experimental model of pacing-induced tachycardia congestive heart failure (CHF), a possible ANS influence on the P wave duration and PR interval oscillations. Approach: Short-term (5 min) time and frequency domain analysis has been obtained in six dogs for the following electrocardiographic intervals: P wave duration (P), from the onset to peak of P wave (Pp), from the onset of P wave to the q onset (PR) and from the end of P wave to the onset of q wave (PeR). Direct vagal nerve activity (VNA), stellate ganglion nerve activity (SGNA) and electrocardiogram (ECG) intervals have been evaluated contextually by implantation of three bipolar recording leads. Main results: At the baseline, multiple regression analysis pointed out that VNA was strongly positively associated with the standard deviation of PP and PeR intervals (r2:0.997, p < 0.05). The same variable was also positively associated with high-frequency (HF) of P expressed in normalized units, of Pp, and of PeR (b: 0.001) (r2: 0.993; p < 0.05). During CHF, most of the time and frequency domain variability significantly decreased from 20% to 50% in comparison to the baseline values (p < 0.05) and SGNA correlated inversely with the low frequency (LF) obtained from PeR (p < 0.05) and PR (p < 0.05) (r2:0.899, p < 0.05). LF components, expressed in absolute and normalized power, obtained from all studied intervals, were reduced significantly during CHF. Any difference between the RR and PP spectral components was observed. Significance: The data showed a significant relationship between ANS and atrial ECG variables, independent of the cycle duration. In particular, the oscillations were vagal mediated at the baseline, while sympathetic mediated during CHF. Whereas P wave variability might have a clinical utility in CHF management, it needs to be addressed in specific studies.

Longitudinal hemodynamic measurements in swine heart failure using a fully implantable telemetry system.

Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment.

Elevated preload is critical for synchronization of myocardial lengthening (é) and mitral inflow (E) in ischemic acute heart failure complicated with tachycardia (1150.2)

Background: Tachycardia in ischemic acute heart failure (AHF) is believed to be a compensatory response to sustain cardiac output and perfusion pressure. Little is known about early diastole in this setting. Methods: In a pig model (n=8,mean±SD) we simultaneously measured myocardial strain (sonometric crystals), mitral-inflow (conductance-catheter) and mitral-pressure difference MITRP (LV-LA micromanometer). Pacing-induced tachycardia was induced in the control state and in ischemic AHF (following coronary microembolization). Results: Tachycardia (160 bpm) shortened the long axis é-delay (see Figure) from 43±30 to 20±21 ms (p=0.0066), compared to E wave in control, but not in AHF (22±13 to 25±17 ms). Interestingly, by reducing preload to similar levels as control, the é-delay became evident also in the AHF condition (22±13 vs 48±23 ms p=0.0067). Additionally, tachycardia increased peak MITRP from 4±1 to 9±4 (p=0.007) mmHg in control, but not in AHF (6±2 to 7±2 mmHg). The enhanced relaxation following tachycardia caused a maintained potential energy across the mitral valve in early filling phase (MITRPINTG) in control (0.4±0.2 to 0.4±0.2 mmHg*s), which was reduced following tachycardia in AHF (0.6±0.2 to 0.4±0.2 mmHg*s p=0.0246). Conclusion: Tachycardia during AHF fails to hasten é and thereby amplifying the pressure driving force across the mitral valve.

Elevated preload is critical for synchronization of myocardial lengthening (é) and mitral inflow (E) in acute ischemic acute heart failure

BackgroundTachycardia in ischemic acute heart failure (AHF) is believed to be a compensatory response to sustain cardiac output and perfusion pressure. Little is known about early diastole in this setting.MethodsIn a pig model (n=8, mean±SD) we simultaneously measured myocardial strain (sonometric crystals), mitral‐inflow (conductance‐catheter) and mitral‐pressure difference MITRP (LV‐LA micromanometer). Pacing‐induced tachycardia was induced in the control state and in ischemic AHF (following coronary microembolization).ResultsTachycardia (160 bpm) shortened the long axis é‐delay (see Figure) from 43±30 to 20±21 ms (p=0.0066), compared to E wave in control, but not in AHF (22±13 to 25±17 ms). Interestingly, by reducing preload to similar levels as control, the é‐delay became evident also in the AHF condition (22±13 vs 48±23 ms p=0.0067). Additionally, tachycardia increased peak MITRP from 4±1 to 9±4 (p=0.007) mmHg in control, but not in AHF (6±2 to 7±2 mmHg). The enhanced relaxation following tachycardia caused a maintained potential energy across the mitral valve in early filling phase (MITRPINTG) in control (0.4±0.2 to 0.4±0.2 mmHg*s), which was reduced following tachycardia in AHF (0.6±0.2 to 0.4±0.2 mmHg*s p=0.0246).ConclusionTachycardia during AHF fails to hasten é and thereby amplifying the pressure driving force across the mitral valve.

Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force–frequency relationship and enhanced poststimulation potentiation

Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a predictor of cardiac events. However, there have been controversies regarding the conditions and mechanisms of MA. To clarify heart rate-dependent contractile properties related to MA, we performed incremental right atrial pacing in 17 idiopathic dilated cardiomyopathy (DCM) patients and in six control patients. The maximal increase in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force gain in the force-frequency relationship (FG-FFR), and the maximal increase in left ventricular dP/dt of the first post-pacing beats was examined as the force gain in poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients (DCM MA(+)) but not in the other 8 DCM patients (DCM MA(-)), and not in any of the control patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 vs 159.4 ± 103.9 mmHg/s, P = 0.0091) and higher FG-PSP (500.0 ± 96.8 vs 321.9 ± 94.9 mmHg/s, P = 0.0017), and accordingly a wider gap between FG-PSP and FG-FFR (465.3 ± 119.4 vs 162.5 ± 123.6 mmHg/s, P = 0.0001) than DCM MA(-) patients. These characteristics of DCM MA(+) showed clear contrasts to those of the control patients. In conclusion, MA is caused with an impaired force-frequency relationship despite significant poststimulation potentiation, suggesting that MA reflects ineffective utilization of the potentiated intrinsic force during tachycardia.

Autonomic Nervous System Activity Measured Directly and QT Interval Variability in Normal and Pacing-Induced Tachycardia Heart Failure Dogs

This study sought to find out more about the relationship between sympathetic and vagal nerve activity and the cardiac repolarization in a canine model of pacing-induced tachycardia congestive heart failure (CHF). The QT variability index (QTVI), a noninvasive marker of temporal cardiac repolarization dispersion, is among the risk factors for sudden death during CHF. Among factors influencing this variable are the myocardial damage and the autonomic nervous system activity typical of dilated cardiomyopathy. We assessed autonomic nervous system activity recorded from an implanted data transmitter that monitored integrated left stellate-ganglion nervous activity, integrated vagus nerve activity, and electrocardiogram. We collected 36 segments recorded at baseline and 36 after induced CHF. We then arbitrarily identified recording segments as containing low or high sympathetic activity values, and we compared corrected QT intervals and the QTVI under a given sympathetic activity condition at baseline and after inducing CHF. In the high sympathetic activity subgroup, both QT variables increased from baseline to CHF (corrected QT intervals, p < 0.01; QTVI, p < 0.05) whereas in the low sympathetic activity subgroup they remained unchanged. The baseline QTVI correlated inversely with integrated vagus nerve activity (r(2) = 0.16; beta = -0.47; p < 0.05) whereas, during CHF, the QTVI correlated directly with integrated left stellate-ganglion nervous activity (r(2) = 0.32; beta = 0.27, p < 0.01). During CHF, sympathetic activation is associated with an increase in the QT interval and QTVI. Because these changes vary over time, they could result from myocardial structural damage and sympathetic activation combined. Conversely, under normal conditions, no relationship exists between sympathetic activation and the QT variables.

Response to Letter Regarding Article, “Interference of Drug-Eluting Stents and Endothelium-Dependent Coronary Vasomotion: Evidence for Device-Specific Responses”

We thank Sabate et al for their interest in our study and agree with a number of points they make. We do not provide a study of the time course of the observed changes. If indeed healing is delayed after implantation of some drug-eluting stents, it is possible that repeat measurements at later time intervals will show the expected, normal vasodilatory response to pacing-induced tachycardia. Instead, we wanted to perform the measurements at 9 to 12 months after implantation when continuation of dual antiplatelet therapy is no longer formally recommended. We do not …

Evaluation of Carotid-Femoral Pulse Wave Velocity

Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. Propagation time is measured variously from the foot of the waveform or point of maximum upslope. We investigated whether these methods give comparable values of PWV at rest, during beta-adrenergic stimulation, and pacing-induced tachycardia. In subjects at rest (n=43), values obtained using the foot-to-foot method (SphygmoCor system) were 1.7+/-0.75 m/s (mean+/-SD) greater than those obtained using the maximum slope (Complior system) at a mean value of 12 m/s. Isoprotenerol (0.5 to 1.5 microg/min; n=10), and pacing (in subjects with permanent pacemakers; n=11) increased heart rate but had differential effects on systolic blood pressure and pulse pressure. The increase in heart rate produced by isoprotenerol (18+/-3 bpm) and pacing (40 bpm) was associated with an increase in PWV measured using both systems (increases of 0.7+/-0.2 m/s and 0.9+/-0.2 m/s for SphygmoCor and Complior, respectively, during isoprotenerol and increases of 2.1+/-0.5 m/s and 1.1+/-0.2 m/s for SphygmoCor and Complior, respectively, during pacing, each P<0.001). Reanalysis of waveforms recorded from the Complior system using the foot-to-foot method produced similar values of PWV to those obtained with the SphygmoCor, confirming that the difference between these systems was attributable to the timing algorithm rather than other aspects of signal acquisition. Carotid-femoral PWV is critically dependent on the method used to determine propagation time, but this does not account for variation of PWV with heart rate.

Internal thoracic artery flow competition: studies in a canine H-graft model.

Internal thoracic artery (ITA) flow competition is a diversion of graft flow through intact ITA branches with a net decrease in perfusion to the grafted coronary. Although a widely acknowledged phenomenon, the conditions under which flow competition occurs have not been established. This is examined in a canine H-graft model. Eight dogs had a right ITA segment interposed (H-graft) between their in situ left ITA (LITA) and the snared left anterior descending (LAD) coronary artery. Proximal LITA and H-graft flows were measured at baseline and during pacing-induced tachycardia, phenylephrine-induced hypertension, and nitroprusside-induced hypotension. Flows were measured with the distal LITA open and occluded. Two additional animals were subjected to eight separate 2-min periods of LAD ischemia, after which post-ischemic H-graft flow measurements were obtained with and without distal LIMA occlusion. During baseline conditions, proximal LITA flow was greater when the distal LITA was open rather than occluded (46+/-15 versus 35+/-12 ml/min, respectively; P=0.002), but H-graft flow did not change significantly (32+/-18 versus 35+/-18 ml/min, respectively; P=0.21). Similarly, occlusion of the distal LITA had no impact on H-graft flow during tachycardia, hypertension, or hypotension. Only in animals subjected to transient LAD ischemia did H-graft flow increase with distal LITA occlusion, albeit marginally (65+/-7-70+/-9 ml/min, occluded versus open, respectively; P=0.04). Mild diversion of flow from the LAD was demonstrated during immediate post-ischemic coronary reperfusion only, and could not be elicited under any other physiologic condition. These data suggest that flow competition is unlikely to constitute a clinically significant limitation to the use of H-grafts or other modalities that leave ITA branches patent.

Myocardial ischemia-reperfusion damage after pacing-induced tachycardia in patients with cardiac syndrome X

The presence of myocardial ischemia in syndrome X (chest pain, "ischemia-like" electrocardiogram changes, and normal coronary angiograms) is uncertain possibly because, when focally distributed, it may not cause contractile dysfunction or lactate production. We measured lipid hydroperoxides (ROOHs) and conjugated dienes (CDs), two sensitive, independent markers of ischemia-reperfusion oxidative stress, in paired aortic and great cardiac vein blood samples before and after pacing-induced tachycardia in nine patients with syndrome X. Diagnostic ischemic S-T segment changes during pacing were followed by a consistent increase in ROOH and CD levels in the great cardiac vein (from 4.83 +/- 1.18 micromol/l at baseline to 7.88 +/- 1.12 micromol/l and from 0.038 +/- 0.002 to 0.051 +/- 0.003 arbitrary units, respectively, P < 0.01). In controls, ROOH and CD levels did not change after pacing. The large postpacing cardiac release of lipid peroxidation products, consistently observed in all patients and similar to that previously observed after ischemia caused by percutaneous transluminal coronary angioplasty, is consistent with an ischemic origin of syndrome X.

Mechanical Function and Substrate Oxidation in the Neonatal Pig Heart Subjected to Pacing-Induced Tachycardia

Isolated, paced, isovolumically beating, neonatal pig (≈2 days) hearts were perfused with a crystalloid solution during four periods: (1) baseline, HR 150 bpm; (2) HR-response curves, HR 150–360 bpm; (3) tachycardia, HR 300 bpm; and (4) posttachycardia, HR 150 bpm. Group I was studied with glucose (5.5 mM) as the sole substrate. During baseline, left ventricular peak systolic pressure (PSP) averaged 123 ± 7 mm Hg; end diastolic pressure (EDP), 4.9 ± 0.4 mm Hg; relaxation time constant (Tau), 29.5 ± 3.9 ms; glucose oxidation (14CO2from [14C]glucose), 1535 ± 96 nmol/min/gdry; and myocardial oxygen consumption (MVO2), 17.4 ± 0.4 μmol/min/gdry. During tachycardia, PSP was 83 ± 4* mm Hg; EDP, 9.8 ± 1.7* mm Hg; Tau, 29.9 ± 5.4 ms; glucose oxidation, 1921 ± 136* nmol/min/gdry; and MVO2, 21.1 ± 0.7* μmol/min/gdry(*different from baseline,P< 0.05). Posttachycardia, all parameters returned to near baseline values, except EDP, which remained elevated. Group II was studied with glucose (5.5 mM) and palmitate (0.55 mM). When compared to those of Group I, the mechanical responses were similar. During baseline, glucose oxidation was 149 ± 24 nmol/min/gdry; palmitate oxidation, 343 ± 28 nmol/min/gdry; and MVO2, 18.4 ± 0.7 μmol/min/gdry. Both oxidation rates increased significantly during tachycardia, indicating aerobic metabolic reserve. Posttachycardia, glucose oxidation returned to baseline, but palmitate oxidation remained elevated, suggesting enhanced beta oxidation. Group III was perfused with glucose (5.5 mM) and pyruvate (5.5 mM), along with iodoacetate (50 μM) to inhibit glycolysis. PSP was maintained, but Tau (HRs ≥ 270 bpm) and EDP (HRs ≥ 180 bpm) markedly increased. In conclusion, for the isovolumically beating, neonatal pig heart stressed with tachycardia: (1) PSP decreases, EDP increases, and Tau remains relatively constant; (2) substrate oxidation is enhanced; and (3) glycolysis, rather than glucose oxidation, appears to be important for supporting ventricular diastolic function.

Balloon mitral valvuloplasty: comparison of haemodynamic and echocardiographic assessment of mitral stenosis at different heart rates in the catheterisation laboratory

Aims: To compare echo-Doppler, Gorlin equation and haemodynamic methods of measuring mitral valve stenosis during right ventricular pacing-induced tachycardia before and after Inoue balloon mitral valvuloplasty to determine which method gave the most consistent results. Methods and results: Measurements were made before and after valvuloplasty at: baseline heart rates, paced at 115 and then 145 beats/min. Mitral valve area by echo-Doppler was 1.1(±0.1) cm 2 (mean±S.E.) before and 1.8(±0.2) cm 2 after valvuloplasty; and by Gorlin equation: 0.9(±0.1) cm 2 before and 1.5(±0.1) cm 2 after. Echo-Doppler measurements were heart rate dependent but those by Gorlin measurements were not. At baseline, cardiac index was 2.08(±0.2) l min −1, left atrial pressure 23.3(±7.9) mmHg and mean mitral diastolic gradient 16.9(±9.9) mmHg. After valvuloplasty, cardiac index was 2.31(±0.1) l min −1, left atrial pressure fell to 19.2(±5.6) mmHg and mean diastolic gradient was reduced to 8.5(±1.8) mmHg. Conclusions: The Gorlin mitral valve area appeared to be the most heart rate independent indicator of success following valvuloplasty.

Effects of pacing-induced and balloon coronary occlusion ischemia on left atrial function in patients with coronary artery disease

OBJECTIVESThe aim of this study was to compare left atrial (LA) function in 16 patients with distal left anterior descending (LAD) and in 16 patients with proximal left circumflex (LCx) coronary artery stenosis at rest and immediately after pacing-induced tachycardia (LAD-pacing [P] and LCx-P) or coronary occlusion (LAD-CO and LCx-CO).BACKGROUNDDuring left ventricular (LV) ischemia, compensatory augmentation of LA contraction enhances LV filling and performance. The left atrium is supplied predominantly by branches arising from the LCx. Therefore, we hypothesized that one mechanism for the loss of atrial contraction may be ischemic LA dysfunction.METHODSLeft ventricular and LA pressure–area relations were derived from simultaneous double-tip micromanometer pressure recordings and automatic boundary detection echocardiograms.RESULTSImmediately after pacing or after coronary occlusion, LV end-diastolic pressure, LV relaxation, LA mean pressure and LV stiffness significantly increased in all patients. However, the area of the A loop of the LA pressure–area relation, representing the LA pump function, significantly decreased in groups LCx-P and LCx-CO (from 14 ± 3 to 9 ± 2, and from 16 ± 4 to 9 ± 2 mm Hg·cm2, respectively, p < 0.05), whereas it increased in groups LAD-P and LAD-CO (from 12 ± 3 to 54 ± 10, and from 16 ± 3 to 49 ± 8 mm Hg·cm2, respectively, p < 0.001).CONCLUSIONSIn patients with LAD stenosis, LV supply or demand ischemia is associated with enhanced LA pump function. However, in patients with proximal LCx stenosis who develop the same type and degree of ischemia, LA branches might have been affected, rendering the LA ischemic and unable to increase its booster pump function.

Beneficial effects of heart rate reduction on cardiac mechanics and energetics in patients with left ventricular dysfunction.

It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO2) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg p.o.). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat(-1) m(-2), p<0.05) at a comparable MVO2 per beat with a marginal increase in LV contractility index (Ees) (from 2.34 to 2.76 mm Hg ml(-1) m(-2), p = 0.08), resulting in a decrease in mechanical efficiency (EW/MVO2) (from 25.9 to 22.1%, p<0.05). In contrast, zatebradine did not decrease Ees (from 2.34 to 2.24 mm Hg ml(-1) m(-2), NS), but increased EW (from 0.39 to 0.42 J beat(-1) m(-2), p<0.05 vs. basal level) without a change in MVO2 per beat, resulting in improved mechanical efficiency (from 25.9 to 29.7%, p<0.05 vs. basal level). These results suggest that mild bradycardia is energetically advantageous and does not decrease myocardial contractility and performance, whereas pacing-induced tachycardia worsens cardiac mechanics and energetics in patients with LV dysfunction. Thus, the oxygen-saving effect of bradycardia may be beneficial for the treatment of heart failure.

Effects of ventricular pacing-induced tachycardia on aortic mechanics in man.

Effects of pacing-induced tachycardia on left ventricular function have been studied extensively. However, little attention has been focused on aortic elastic properties during heart rate increments. The aim was to determine the effects of right ventricular pacing on the aortic elastic properties. We studied 14 normal subjects (baseline blood pressure, 129/84 +/- 10/6 mmHg; aortic diameter, 23.5/21.3 +/- 2.4/1.9 mm) at rest, during rapid right ventricular pacing (at five stepwise heart rate increases of 20 bpm every 2 min) and after 5 min recovery. Shifts as well as changes in the slope and the stiffness constant of the pressure diameter (p-d) relation, derived from simultaneous tip-micromanometer aortic pressure recordings and high-fidelity ultrasonic intravascular aortic diameter recordings, were used as indices of aortic stiffness. Wave reflection was also studied. Aortic pulse pressure and strain significantly decreased after pacing-induced tachycardia (p < 0.0001 and < 0.05, respectively). During pacing, the slope of the linear p-d relation as well as the stiffness constant were decreased, followed by increases at recovery (p < 0.0001). The augmentation index and the aortoventricular coupling ratio were significantly decreased (p < 0.0001). Pacing-induced increases in pulse frequency may result in improved aortic distensibility and aortoventricular coupling.

Role of microtubules in the contractile dysfunction of myocytes from tachycardia-induced dilated cardiomyopathy.

Microtubules of cardiac myocytes are increased in pressure-overloaded cardiac hypertrophy, which interfere with the actin-myosin crossbridge motion and depress muscle contractility. However, it is unknown whether microtubules are increased in non-hypertrophied, dilated cardiomyopathy and, if so, their increase could contribute to the depressed contractility. We assessed the contractile function of isolated left-ventricular (LV) myocytes and also quantitated tubulin mRNA levels as well as free and polymerized tubulin proteins using the LV myocardium obtained from dogs with rapid pacing (240 beats/min, 4 weeks)-induced dilated failing cardiomyopathy (HF; n = 6) and control dogs (n = 6). Myocyte contractility was significantly depressed in HF compared to control. Northern blot analysis indicated that tubulin mRNA levels (normalized to GAPDH mRNA) in HF dogs were upregulated (0.43 +/- 0.04 v 0.13 +/- 0.02; P < 0.01). In contrast, the amount of total tubulins (633 +/- 52 v 697 +/- 42 micrograms/g wet weight; P = N.S.) and the ratio of polymerized tubulin fraction-to-total tubulin (0.44 +/- 0.02 v 0.44 +/- 0.01; P = N.S.) did not differ between the two groups. Immunohistochemical studies showed no apparent differences in the distribution or density of intracellular microtubule network. Further, the exposure of myocytes to colchicine (1 mumol/l, 30 min), which depolymerizes microtubules, did not promote any improvement of the depressed myocyte contraction. Pacing-induced tachycardia increased myocardial tubulin mRNA, but the amount of total and polymerized tubulins were not increased, indicating that alterations in myocyte microtubules do not contribute to the contractile abnormalities in this model of HF.

Left ventricular inotropic and lusitropic responses to pacing-induced tachycardia in patients with varying degrees of ventricular dysfunction

Background: In the failing human heart contractile reserve during tachycardia is attenuated or absent. However, it is not known whether during tachycardia diminished inotropic reserve depends on the degree of ventricular dysfunction or lusitropic reserve is also diminished in patients with left ventricular (LV) dysfunction. Methods: We studied 18 patients with dilated cardiomyopathy or mildly depressed LV function and 13 subjects in a control group (ejection fraction 0.67 ± 0.09). The patients were classified into two groups based on whether their ejection fraction was less than or more than 0.40 (group 1, ejection fraction 0.27 ± 0.05; group 2, ejection fraction 0.49 ± 0.07). LV pressures were measured with a catheter-tip manometer during incremental right atrial pacing up to a heart rate of 150 beats/min. Results: With incremental pacing LV peak positive dP/dt rose progressively in both the normal group and in group 2, but the increase was less for group 2 than for the normal group; in group 1 the increase was slight or absent. In contrast, a significant and progressive decrease occurred in the time constant of LV relaxation in all three groups. Although their values remained significantly different at each heart rate, no intergroup differences in absolute or percent changes were present. Conclusions: These findings suggest that during tachycardia LV inotropic reserve may be diminished depending on the degree of ventricular dysfunction, and lusitropic reserve may be preserved in patients with depressed function despite an attenuated inotropic response. (Am Heart J 1998;135:584-91.)

What Can We Learn from Provoking Ischemia?

What Can We Learn from Provoking Ischemia?