Ca2+ transient decline and myocardial relaxation are slowed during low flow ischemia in rat hearts

Area of Science:

• Cardiovascular Physiology
• Cardiac Metabolism
• Myocardial Ischemia Research

Background:

• Myocardial relaxation impairment during ischemia is suspected to involve calcium handling issues.
• Direct evidence linking calcium handling to impaired relaxation during ischemia is limited.

Purpose of the Study:

• To investigate if the time constant of cytosolic calcium ([Ca2+]c) decline (tau Ca) increases during low-flow ischemia.
• To determine the relationship between tau Ca and the time constant of left ventricular pressure decline (tau P), an indicator of myocardial relaxation.

Main Methods:

• Isolated perfused hearts were utilized to measure cytosolic calcium ([Ca2+]c) using the indo-1 fluorescence ratio.
• The time constant of left ventricular pressure decline (tau P) served as the index for myocardial relaxation.
• Indo-1 transients were calibrated to calculate tau Ca under varying levels of reduced coronary flow.

Main Results:

• The time constant of the indo-1 ratio (representing [Ca2+]c decline) significantly increased as coronary flow was reduced.
• Calculated tau Ca also showed a marked increase at 20% and 10% of control coronary flow.
• A strong linear relationship (r = 0.82) was observed between tau Ca and tau P.

Conclusions:

• The findings support the hypothesis that impaired myocardial relaxation during low-flow ischemia is associated with a slowing of cytosolic calcium ([Ca2+]c) decline.
• Abnormalities in calcium handling, specifically delayed calcium extrusion, contribute to diastolic dysfunction under ischemic conditions.
• This study provides direct evidence linking altered intracellular calcium dynamics to impaired cardiac relaxation during ischemia.