Spatial Heterogeneity of Calcium Transient Alternans During the Early Phase of Myocardial Ischemia in the Blood-Perfused Rabbit Heart

Abstract

Background-Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca 2ϩ ] i indicators. We propose that beat-to-beat [Ca 2ϩ ] i transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents. Methods and Results-To test this hypothesis, isolated rabbit hearts were loaded with the fluorescent [Ca 2ϩ ] i indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca 2ϩ ] i transients were recorded in each of 8 hearts. [Ca 2ϩ ] i transient alternans was never present in control records but occurred in each of the hearts during ischemia, with onset after 2 to 4 minutes. Alternans was confined to circumscribed regions of the heart surface 5 to 15 mm across. Multiple regions of alternans were found in most hearts, and regions that were out of phase with one another were found in 6 hearts. Quantitative maps of alternans were constructed by calculating an alternans ratio. This ratio behaved as a continuous variable that reached a maximum value in the center of the regions with alternans.Conclusions-These results demonstrate marked spatial heterogeneity of the [Ca 2ϩ ] i transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts. (Circulation. 2001;

Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca 2+ Transient in Rat Ventricular Myocytes

“…17,24,28,29 Recently, regions comprising several cells have been found to alternate in phase but out of phase with other regions. 30 The present study shows that tetracaine or acidification can result in a small degree of alternans at the whole cell level (Figures 2 and 6). One novel result is that, under these conditions, alternating Ca 2ϩ release is more obvious at the subcellular level where regions of the order of tens of microns alternate out of phase with each other.…”

Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart

“…The experiments reported here utilized the same experimental model and recording apparatus used by Qian et al (30) alternans was confined to specific regions of the heart surface, and multiple regions, which were out of phase and separated by a boundary, could be present in the same heart. Circumscribed regions of [Ca 2ϩ ] i transient alternans were as small as 5 mm and quantitative maps could be constructed using an alternans ratio.…”

“…Thus it is likely that most or all of the hearts had regions where APD alternans was out of phase. Qian et al (30) found Ca 2ϩ transient alternans in each of the eight ischemic hearts studied with rhod-2, with regions where alternans was out of phase in six of the eight hearts. Because rhod-2 has a considerably better signal-to-noise ratio than di-4-ANEPPS, the ability to detect alternans and the completeness of the alternans maps would be better with rhod-2.…”

“…These dyes can be used in conjunction with high-resolution imaging cameras to obtain recordings from hundreds or thousands of pixels simultaneously (24). Fluorescence imaging has been used to map Ca 2ϩ transient alternans during ischemia in the blood-perfused rabbit heart (30), and marked spatial heterogeneity was found. Optical methods have also been used to study the mechanism of electrical defibrillation in the presence and absence of ischemia in hearts taken from small mammals (4,13,15).…”

Decreasing motion artifacts in calcium-dependent fluorescence transients from the perfused mouse heart using frequency filtering

“…The use of absorption measurements at Rhod-2-sensitive wavelengths can be used to quantify relative levels of calcium [5,6]. There is growing interest in using Rhod-2 to measure calcium transients from the intact heart [5][6][7][21][22][23][24]. To decrease the influence of motion, in this study we have developed a technique to filter motion artifacts from the fluorescence signal in the frequency domain using the shift theorem of Fourier analysis which is independent of the time-shift error that may occur in the motion reference signal.…”